88 results on '"Ruchuan Liu"'
Search Results
2. SKPM study on organic-inorganic perovskite materials
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Kena Song, Yinghui Wu, Xi Chen, Yi He, Liyu Liu, Guo Chen, and Ruchuan Liu
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Physics ,QC1-999 - Abstract
We report Atomic Force Microscopy (AFM) and Scanning Kelvin Probe Microscopy (SKPM) studies on the surface morphology and surface potential properties of CH3NH3PbI3, CH3NH3PbI3-xClx, CH3NH3PbI3-xBrx and CH3NH3PbBr3-xClx, respectively. For CH3NH3PbI3 rod structure, its surface potential is independent of the precursor concentration, suggesting a robust electronic feature. Surface potential studies of CH3NH3PbI3 particle reveal that the Fermi level within CH3NH3PbI3 is strongly influenced by the substrate. In the case of CH3NH3PbI3-xClx, its surface potential depends on precursor concentrations and we suspect that chlorine concentrated solutions might lead to more chlorine incorporation in the final products, thus lowering its Fermi level. Also, we studied the surface potentials of CH3NH3PbI3-xBrx and CH3NH3PbBr3-xClxwith specified halide ratios. The surface potential differences between different samples are related to their work function variations. These results are helpful to the understanding of the structural and electronic properties of perovskite materials.
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- 2018
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3. Modeling three-dimensional invasive solid tumor growth in heterogeneous microenvironment under chemotherapy.
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Hang Xie, Yang Jiao, Qihui Fan, Miaomiao Hai, Jiaen Yang, Zhijian Hu, Yue Yang, Jianwei Shuai, Guo Chen, Ruchuan Liu, and Liyu Liu
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Medicine ,Science - Abstract
A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations indicate that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization.
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- 2018
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4. Hybrid Organic/Inorganic Nanocomposites for Photovoltaic Cells
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Ruchuan Liu
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solar cell ,semiconductor ,conjugated polymer ,nanostructure ,photovoltaic ,charge separation ,interface ,nanocomposites ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
Inorganic/organic hybrid solar cells have attracted a lot of interest due to their potential in combining the advantages of both components. To understand the key issues in association with photoinduced charge separation/transportation processes and to improve overall power conversion efficiency, various combinations with nanostructures of hybrid systems have been investigated. Here, we briefly review the structures of hybrid nanocomposites studied so far, and attempt to associate the power conversion efficiency with these nanostructures. Subsequently, we are then able to summarize the factors for optimizing the performance of inorganic/organic hybrid solar cells.
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- 2014
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5. Microfabrication-Based Three-Dimensional (3-D) Extracellular Matrix Microenvironments for Cancer and Other Diseases
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Kena Song, Zirui Wang, Ruchuan Liu, Guo Chen, and Liyu Liu
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microfabrication ,extracellular matrix ,cancer ,metastasis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Exploring the complicated development of tumors and metastases needs a deep understanding of the physical and biological interactions between cancer cells and their surrounding microenvironments. One of the major challenges is the ability to mimic the complex 3-D tissue microenvironment that particularly influences cell proliferation, migration, invasion, and apoptosis in relation to the extracellular matrix (ECM). Traditional cell culture is unable to create 3-D cell scaffolds resembling tissue complexity and functions, and, in the past, many efforts were made to realize the goal of obtaining cell clusters in hydrogels. However, the available methods still lack a precise control of cell external microenvironments. Recently, the rapid development of microfabrication techniques, such as 3-D printing, microfluidics, and photochemistry, has offered great advantages in reconstructing 3-D controllable cancer cell microenvironments in vitro. Consequently, various biofunctionalized hydrogels have become the ideal candidates to help the researchers acquire some new insights into various diseases. Our review will discuss some important studies and the latest progress regarding the above approaches for the production of 3-D ECM structures for cancer and other diseases. Especially, we will focus on new discoveries regarding the impact of the ECM on different aspects of cancer metastasis, e.g., collective invasion, enhanced intravasation by stress and aligned collagen fibers, angiogenesis regulation, as well as on drug screening.
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- 2018
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6. Biophysical properties of intrinsically disordered p130Cas substrate domain--implication in mechanosensing.
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Kinya Hotta, Soumya Ranganathan, Ruchuan Liu, Fei Wu, Hiroaki Machiyama, Rong Gao, Hiroaki Hirata, Neelesh Soni, Takashi Ohe, Christopher W V Hogue, M S Madhusudhan, and Yasuhiro Sawada
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Biology (General) ,QH301-705.5 - Abstract
Mechanical stretch-induced tyrosine phosphorylation in the proline-rich 306-residue substrate domain (CasSD) of p130Cas (or BCAR1) has eluded an experimentally validated structural understanding. Cellular p130Cas tyrosine phosphorylation is shown to function in areas without internal actomyosin contractility, sensing force at the leading edge of cell migration. Circular dichroism shows CasSD is intrinsically disordered with dominant polyproline type II conformations. Strongly conserved in placental mammals, the proline-rich sequence exhibits a pseudo-repeat unit with variation hotspots 2-9 residues before substrate tyrosine residues. Atomic-force microscopy pulling experiments show CasSD requires minimal extension force and exhibits infrequent, random regions of weak stability. Proteolysis, light scattering and ultracentrifugation results show that a monomeric intrinsically disordered form persists for CasSD in solution with an expanded hydrodynamic radius. All-atom 3D conformer sampling with the TraDES package yields ensembles in agreement with experiment when coil-biased sampling is used, matching the experimental radius of gyration. Increasing β-sampling propensities increases the number of prolate conformers. Combining the results, we conclude that CasSD has no stable compact structure and is unlikely to efficiently autoinhibit phosphorylation. Taking into consideration the structural propensity of CasSD and the fact that it is known to bind to LIM domains, we propose a model of how CasSD and LIM domain family of transcription factor proteins may function together to regulate phosphorylation of CasSD and effect machanosensing.
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- 2014
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7. The value of VI-RADS combined with tumor contact length in the detection of muscle-invasive bladder cancer
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CHEN Ruchuan, LIU Wei, ZHOU Bingni, LIU Xiaohang, ZHOU Liangping
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vesical imaging-reporting and data system ,tumor contact length ,muscle-invasive bladder cancer ,magnetic resonance imaging ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background and purpose: The value of Vesical Imaging-Reporting and Data System (VI-RADS) based on multiparametric magnetic resonance imaging (MRI) in the preoperative assessment of bladder cancer muscle-invasive is increasingly recognized. However, there is still a high number of false positives when the diagnostic cut-off value is 3 points. Tumor size has certain auxiliary diagnostic value in the assessment of tumor infiltration. Therefore, this study mainly explored the diagnostic performance of VI-RADS combined with tumor size in assessing bladder cancer muscle-invasive. Methods: The preoperative bladder multiparametric MRI and clinical data of 119 patients with bladder cancer confirmed by surgery and pathology (a total of 159 lesions) who were treated in Fudan University Shanghai Cancer Center from November 2019 to February 2022 were retrospectively collected. VI-RADS score and tumor contact length (TCL) measurements were performed independently for each lesion by two radiologists. Lesions with differences in score or size were given consistent results following discussion by two physicians. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of VI-RADS, TCL and their combined models for muscle invasion, and the corresponding area under curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were compared. Results: Postoperative pathology confirmed that there were 75 and 84 lesions of non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), respectively. The mean TCL of MIBC group (6.15-6.23 cm) was significantly different from that of NMIBC group (2.26-2.35 cm), and the difference was statistically significant (P0.05). There was no significant difference in AUC between TCL (AUC = 0.89), VI-RADS (AUC = 0.90) and VI-RADS combined with TCL (AUC = 0.91) (P>0.05). Conclusion: VI-RADS combined with TCL can reduce the false positive rate of VI-RADS 3-point lesions in the evaluation of bladder cancer muscle-invasive to a certain extent, which is beneficial for avoiding overtreatment.
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- 2023
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8. Single molecule fluorescence spectroscopy for quantitative biological applications.
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Ruchuan Liu, Yuliang Li, and Liyu Liu
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- 2016
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9. Poor Prognosis With Coexistence Of EGFR T790M Mutation And Common EGFR-Activating Mutation In Non- Small Cell Lung Cancer
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Zhengquan Yu, Xuejuan Gao, Jianwei Shuai, Wei Yin, Liyu Liu, Xiao Zhou, Ruchuan Liu, Yanfeng Zhao, and Yi Bao
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Odds ratio ,medicine.disease ,respiratory tract diseases ,Metastasis ,03 medical and health sciences ,T790M ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Mutation (genetic algorithm) ,medicine ,Adenocarcinoma ,EGFR Activating Mutation ,business ,Lung cancer ,Tyrosine kinase - Abstract
Purpose Previous studies have shown that the presence of EGFR T790M mutation may reduce the treatment efficacy of tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer. However, little is known about the clinical features and outcomes of EGFR T790M mutation in pretreated patients with NSCLC. Patients and methods The clinical features of EGFR-activating and T790M mutations were assessed in a large cohort of patients with EGFR-TKI-naive NSCLC (all/EGFR mutations, n=16,347/7,687). The correlation between the pretreatment T790M mutation status and clinical outcomes was evaluated using univariate and multivariate analyses. Results Pretreatment T790M mutation was reported in 1.39% of the patients and coexisted with an EGFR-activating or uncommon mutation. The dual EGFR T790M and common EGFR-activating mutations were more likely to be detected in lung adenocarcinoma, whereas single T790M mutation was more prevalent in non-adenocarcinomas. The presence of de novo T790M mutation correlated with reduced recurrence-free survival (RFS) in patients with NSCLC (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.67-6.79, P = 0.001). After molecular stratification, T790M mutation was shown to exert adverse effects on the RFS of EGFR 19-del group (OR 2.89, 95% CI 1.10-7.91, P = 0.028) and EGFR L858R group (OR 3.43, 95% CI 1.33-8.88, P = 0.013). Furthermore, pretreatment T790M mutation promoted tumor metastasis to different sites. Conclusion T790M-positive tumors presented special clinical features, and the coexistence of T790M and common EGFR-activating mutations was associated with poor prognosis in patients with NSCLC.
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- 2019
10. Multifunctional atomic force probes for Mn2+ doped perovskite solar cells
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Yinghui Wu, Wei Chen, Zunyuan Wan, Zhubing He, Xiyuan Feng, Aleksandra B. Djurišić, Liyu Liu, Guo Chen, and Ruchuan Liu
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Materials science ,Dopant ,Renewable Energy, Sustainability and the Environment ,Open-circuit voltage ,Band gap ,business.industry ,Doping ,Energy Engineering and Power Technology ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Scanning probe microscopy ,Semiconductor ,Optoelectronics ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,0210 nano-technology ,business ,Short circuit ,Perovskite (structure) - Abstract
Doping in organic–inorganic perovskite semiconductors is an effective method to tailor their optoelectronic properties. In this work, manganese-doped perovskite films with different Mn/Pb ratios ranging from 0% to 2% were systematically studied. The device performance of 0.2% Mn-doped devices was improved compared to that of a device without Mn. However, a further increase of the doping concentration induced a decrease in performance. Several characteristics (especially different scanning probe microscopy characteristics) reveal that an increased dopant concentration results in reduced crystallinity and a change in the film morphology and causes a deterioration in photovoltaic performance for higher dopant concentrations. In the best-performing samples (0.2%), a shift in the valence band level and band gap are found which are responsible for the increased open circuit voltage, while increased grain boundaries and lower surface charge density are responsible for a small reduction in the short circuit current. Thus, multifunctional scanning probe microscopy approaches, combined with different film characterization techniques, offer us effective tools to investigate the impact of doping in the perovskite materials and the corresponding device performance.
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- 2019
11. A highly [001]-textured Sb2Se3 photocathode for efficient photoelectrochemical water reduction
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Xiangnan Gong, Lingfei Cao, Kena Song, Hongpeng Zhou, Dingke Zhang, Shijian Chen, Bin Liao, Menglei Feng, Yichang Wang, and Ruchuan Liu
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Photocurrent ,Materials science ,business.industry ,02 engineering and technology ,Solar illumination ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Photocathode ,0104 chemical sciences ,Reduction (complexity) ,Optoelectronics ,Water splitting ,General Materials Science ,0210 nano-technology ,business - Abstract
Anisotropic Sb2Se3 is an emerging earth-abundant photocathode for photoelectrochemical water splitting. However, controlling the growth of the Sb2Se3 film with optimal [001] crystallographic orientation is still the most challenging issue. Here, we successfully synthesized [001]-oriented Sb2Se3via a reliable and facile method. The [001]-oriented Sb2Se3 film could provide an excellent carrier-migration efficiency. Consequently, we achieved a record-high photocurrent density of -20.2 mA cm-2 at 0 VRHE and a very high half-cell solar-to-hydrogen efficiency of 1.36% under 1-sun simulated solar illumination in a TiO2/[001]-Sb2Se3 photocathode. This work provides an effective strategy and important guidelines for rationally designing optoelectronic devices based on the [001]-oriented Sb2Se3 film.
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- 2019
12. A highly [001]-textured Sb
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Hongpeng, Zhou, Menglei, Feng, Kena, Song, Bin, Liao, Yichang, Wang, Ruchuan, Liu, Xiangnan, Gong, Dingke, Zhang, Lingfei, Cao, and Shijian, Chen
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Anisotropic Sb
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- 2019
13. Motile parameters of cell migration in anisotropic environment derived by speed power spectrum fitting with double exponential decay
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Xuejuan Gao, Ruchuan Liu, Jing Qu, Qingzu He, Yanping Liu, Xiang Li, Jianwei Shuai, and Liyu Liu
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Physics ,Physics and Astronomy (miscellaneous) ,Quantitative Biology::Tissues and Organs ,Mathematical analysis ,Double exponential function ,Spectral density ,Random walk ,01 natural sciences ,Spectral line ,Quantitative Biology::Cell Behavior ,Power (physics) ,Langevin equation ,0103 physical sciences ,Perpendicular ,010306 general physics ,Anisotropy - Abstract
Cell migration through anisotropic microenvironment is critical to a wide variety of physiological and pathological processes. However, adequate analytical tools to derive motile parameters to characterize the anisotropic migration are lacking. Here, we proposed a method to obtain the four motile parameters of migration cells based on the anisotropic persistent random walk model which is described by two persistence times and two migration speeds at perpendicular directions. The key process is to calculate the velocity power spectra of cell migration along intrinsically perpendicular directions respectively, then to apply maximum likelihood estimation to derive the motile parameters from the power spectra fitting with double exponential decay. The simulation results show that the averaged persistence times and the corrected migration speeds can be good estimations for motile parameters of cell migration.
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- 2019
14. General Method To Define the Type of Carrier Transport Materials for Perovskite Solar Cells via Kelvin Probes Microscopy
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Zhenggang Wu, Wei Chen, Zhubing He, Yinghui Wu, Yi Lin, Ruchuan Liu, Bao Tu, Xiaoqi Lan, and Aleksandra B. Djurišić
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Photoluminescence ,Materials science ,business.industry ,Photovoltaic system ,Non-blocking I/O ,Energy Engineering and Power Technology ,02 engineering and technology ,Electron ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Microscopy ,Materials Chemistry ,Electrochemistry ,Chemical Engineering (miscellaneous) ,Optoelectronics ,Grain boundary ,Electrical and Electronic Engineering ,0210 nano-technology ,business ,Perovskite (structure) ,Voltage - Abstract
Various kinds of semiconductor materials, organic and inorganic, served effectively as electrons or holes transport materials for perovskite solar cells (PSCs). However, their direct function has rarely been reported other than examining their effect in the final photovoltaic devices. In this work, a general and facile method was employed to determine to a point the type of carriers transferred by both SnO2 and NiO popular charge transport materials in PSCs via scanning Kelvin probes microscopy. The sign of the increment of the surface potential voltage measured tells directly whether electrons or holes were extracted by these carrier transport materials while its mapping can also provide the extraction difference between grain interiors and grain boundaries. Both MAPbI3 and CsFAMA triple cation perovskites were involved in the test with the same conclusion. Along with time-resolved photoluminescence, the extraction rate of each kind of material can be distinguished. This work definitely offers us a gener...
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- 2018
15. Diversity of collective migration patterns of invasive breast cancer cells emerging during microtrack invasion
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Zhijian Hu, Liyu Liu, Weijing Han, Junle Qu, Ruchuan Liu, Kena Song, Xuefeng Jiang, Shaohua Chen, Yu Zheng, Jianwei Shuai, Yong Liao, Hongfei Zhang, Yang Jiao, Wenbin Cao, and Hanqing Nan
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Matrigel ,Tumor microenvironment ,Breast Neoplasms ,Biology ,Models, Biological ,01 natural sciences ,Phenotype ,Cellular automaton ,010305 fluids & plasmas ,Cell biology ,Collective migration ,Multicellular organism ,Cell Movement ,Tissue Array Analysis ,0103 physical sciences ,Tumor Microenvironment ,Humans ,Neoplasm Invasiveness ,Breast cancer cells ,010306 general physics ,Extracellular Matrix Degradation - Abstract
Understanding the mechanisms underlying the diversity of tumor invasion dynamics, including single-cell migration, multicellular streaming, and the emergence of various collective migration patterns, is a long-standing problem in cancer research. Here we have designed and fabricated a series of microchips containing high-throughput microscale tracks using protein repelling coating technology, which were then covered with a thin Matrigel layer. By varying the geometrical confinement (track width) and microenvironment factors (Matrigel concentration), we have reproduced a diversity of collective migration patterns in the chips, which were also observed in vivo. We have further classified the collective patterns and quantified the emergence probability of each class of patterns as a function of microtrack width and Matrigel concentration to devise a quantitive "collective pattern diagram." To elucidate the mechanisms behind the emergence of various collective patterns, we employed cellular automaton simulations, incorporating the effects of both direct cell-cell interactions and microenvironment factors (e.g., chemical gradient and extracellular matrix degradation). Our simulations suggest that tumor cell phenotype heterogeneity, and the associated dynamic selection of a favorable phenotype via cell-microenivronment interactions, are key to the emergence of the observed collective patterns in vitro.
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- 2019
16. Modeling cell migration regulated by cell extracellular-matrix micromechanical coupling
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Qihui Fan, Yanping Liu, Yu Zheng, Ruchuan Liu, Xiaochen Wang, Bo Sun, Fangfu Ye, Yang Jiao, Liyu Liu, and Hanqing Nan
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Stochastic Processes ,Tractive force ,Durotaxis ,Chemistry ,Cell ,Cell migration ,01 natural sciences ,Models, Biological ,010305 fluids & plasmas ,Biomechanical Phenomena ,Cell Line ,Extracellular Matrix ,Focal adhesion ,Extracellular matrix ,Multicellular organism ,medicine.anatomical_structure ,Cell Movement ,0103 physical sciences ,medicine ,Biophysics ,Humans ,010306 general physics ,Actin ,Mechanical Phenomena - Abstract
Cell migration in fibrous extracellular matrix (ECM) is crucial to many physiological and pathological processes such as tissue regeneration, immune response, and cancer progression. During migration, individual cells can generate active pulling forces via actomyosin contraction, which are transmitted to the ECM fibers through focal adhesion complexes, remodel the ECM, and eventually propagate to and can be sensed by other cells in the system. The microstructure and physical properties of the ECM can also significantly influence cell migration, e.g., via durotaxis and contact guidance. Here, we develop a computational model for two-dimensional cell migration regulated by cell-ECM micromechanical coupling. Our model explicitly takes into account a variety of cellular-level processes, including focal adhesion formation and disassembly, active traction force generation and cell locomotion due to actin filament contraction, transmission and propagation of tensile forces in the ECM, as well as the resulting ECM remodeling. We validate our model by accurately reproducing single-cell dynamics of MCF-10A breast cancer cells migrating on collagen gels and show that the durotaxis and contact guidance effects naturally arise as a consequence of the cell-ECM micromechanical interactions considered in the model. Moreover, our model predicts strongly correlated multicellular migration dynamics, which are resulted from the ECM-mediated mechanical coupling among the migrating cell and are subsequently verified in in vitro experiments using MCF-10A cells. Our computational model provides a robust tool to investigate emergent collective dynamics of multicellular systems in complex in vivo microenvironment and can be utilized to design in vitro microenvironments to guide collective behaviors and self-organization of cells.
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- 2019
17. Biomechanics of Collective Cell Migration in Cancer Progression -- Experimental and Computational Methods
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Ruchuan Liu, Zi Chen, Jing Fan, Hao Zhang, Qiaohang Guo, Xinyue Han, Jacob Notbohm, Dung Trung Nguyen, Catalina-Paula Spatarelu, and Liyu Liu
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In silico ,0206 medical engineering ,Biomedical Engineering ,FOS: Physical sciences ,02 engineering and technology ,Biology ,Article ,Biomaterials ,Extracellular matrix ,Cell Behavior (q-bio.CB) ,medicine ,Epithelial–mesenchymal transition ,Physics - Biological Physics ,Mechanism (biology) ,Collective cell migration ,Cancer ,Cell migration ,021001 nanoscience & nanotechnology ,medicine.disease ,020601 biomedical engineering ,Review article ,Biological Physics (physics.bio-ph) ,FOS: Biological sciences ,Quantitative Biology - Cell Behavior ,0210 nano-technology ,Neuroscience - Abstract
Cell migration is essential for regulating many biological processes in physiological or pathological conditions, including embryonic development and cancer invasion. In vitro and in silico studies suggest that collective cell migration is associated with some biomechanical particularities such as restructuring of extracellular matrix (ECM), stress and force distribution profiles, and reorganization of the cytoskeleton. Therefore, the phenomenon could be understood by an in-depth study of cells' behavior determinants, including but not limited to mechanical cues from the environment and from fellow "travelers". This review article aims to cover the recent development of experimental and computational methods for studying the biomechanics of collective cell migration during cancer progression and invasion. We also summarized the tested hypotheses regarding the mechanism underlying collective cell migration enabled by these methods. Together, the paper enables a broad overview on the methods and tools currently available to unravel the biophysical mechanisms pertinent to cell collective migration as well as providing perspectives on future development toward eventually deciphering the key mechanisms behind the most lethal feature of cancer.
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- 2019
18. Single molecule fluorescence spectroscopy for quantitative biological applications
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Yuliang Li, Liyu Liu, and Ruchuan Liu
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0301 basic medicine ,chemistry.chemical_classification ,Chemistry ,Applied Mathematics ,Biomolecule ,Nanotechnology ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Single-molecule experiment ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Force sensor ,Computer Science Applications ,03 medical and health sciences ,Molecular dynamics ,030104 developmental biology ,Molecular level ,Modeling and Simulation ,Molecular mechanism ,0210 nano-technology ,Spectroscopy - Abstract
Single molecule techniques emerge as powerful and quantitative approaches for scientific investigations in last decades. Among them, single molecule fluorescence spectroscopy (SMFS) is able to non-invasively characterize and track samples at the molecular level. Here, applications of SMFS to fundamental biological questions have been briefly summarized in catalogues of single-molecule counting, distance measurements, force sensors, molecular tracking, and ultrafast dynamics. In these SMFS applications, statistics and physical laws are utilized to quantitatively analyze the behaviors of biomolecules in cellular signaling pathways and the mechanisms of biological functions. This not only deepens our understanding of bio-systems, but also provides a fresh angle to those fundamental questions, leading to a more quantitative thinking in life science.
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- 2016
19. 'Nano-Fishnet' Structure Making Silk Fibers Tougher
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Daiwen Yang, Ming-Yong Han, Xiang-Yang Liu, Zhen Yang, Ruchuan Liu, and Qinqiu Deng
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Diffraction ,Toughness ,Materials science ,Polymer science ,Force spectroscopy ,Stacking ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,Electronic, Optical and Magnetic Materials ,Biomaterials ,SILK ,Synthetic fiber ,Nano ,Electrochemistry ,0210 nano-technology ,Topology (chemistry) - Abstract
Based on the combined technologies of atomic force microscopy, X-ray diffraction/scattering, Fourier transform infrared spectra analysis, etc., it is demonstrated that the nano-fishnet-like networks, one of the most flexible but toughest structures, turn out to be the basic structure of silk filaments. The force patterns of pulling individual fibrils allow the identification of the pathways of unfolding protein segments in stacking β-crystallites, which reveal the fishnet-like topology. The calculation shows that the β-crystallites in silk nanofibrils are the cross-linking points of the nano-fishnets, which may enhance the toughness of silk filaments up to 1000 times, compared with amyloid-like and unlinked string structures. It follows that the strong β-sheet–β-sheet interaction, a high degree of ordering, and a high density of β-crystallites in silk fibers toughen the fishnet structure, then strengthen silk filaments, in consistency with the experiments for both spider and silkworm silks. The knowledge on the fishnet structure of silk fibers sheds light on the design and synthesis of either protein or synthetic fibers of ultraperformance in a more generic way.
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- 2016
20. Uncovering mechanosensing mechanisms at the single protein level using magnetic tweezers
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Ruchuan Liu, Shimin Le, Chwee Teck Lim, and Jie Yan
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Talin ,0301 basic medicine ,Magnetic tweezers ,Alpha catenin ,Biology ,Mechanotransduction, Cellular ,General Biochemistry, Genetics and Molecular Biology ,Focal adhesion ,Adherens junction ,03 medical and health sciences ,Cytoskeleton ,Molecular Biology ,Focal Adhesions ,Protein Stability ,Cell adhesion molecule ,Magnetic Phenomena ,Electron Spin Resonance Spectroscopy ,Vinculin ,equipment and supplies ,Extracellular Matrix ,Cell biology ,030104 developmental biology ,Biophysics ,biology.protein ,Mechanosensitive channels ,Cell Adhesion Molecules ,human activities ,alpha Catenin - Abstract
Mechanosensing of the micro-environments has been shown to be essential for cell survival, growth, differentiation and migration. The mechanosensing pathways are mediated by a set of mechanosensitive proteins located at focal adhesion and cell-cell adherens junctions as well as in the cytoskeleton network. Here we review the applications of magnetic tweezers on elucidating the molecular mechanisms of the mechanosensing proteins. The scope of this review includes the principles of the magnetic tweezers technology, theoretical analysis of force-dependent stability and interaction of mechanosensing proteins, and recent findings obtained using magnetic tweezers.
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- 2016
21. Charges on nano-islands and fibrils of poly(3-hexylthiophene-2,5-diyl) – light-modulation, injection and transportation
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Xi Chen, Yuenan Li, Ruchuan Liu, Yinghui Wu, Haixia Xuan, and Kena Song
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chemistry.chemical_classification ,Materials science ,Nanostructure ,General Chemical Engineering ,Electrostatic force microscope ,Stacking ,Analytical chemistry ,02 engineering and technology ,General Chemistry ,Polymer ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Crystallinity ,symbols.namesake ,chemistry ,Chemical physics ,Nano ,symbols ,Molecule ,0210 nano-technology ,Raman spectroscopy - Abstract
The impact of the nanostructures of conjugated polymers on their electronic properties is significant. We notice that poly(3-hexylthiophene-2,5-diyl) (P3HT) can form nano-islands and nano-fibrils, and both of them show an similar single-layer thickness (∼1.5–1.6 nm) as evaluated by atomic force microscopy (AFM). The Raman spectra indicate the highest degree of chain planarity and crystallinity in the nano-islands. By using scanning Kelvin probe microscopy (SKPM) and electrostatic force microscopy (EFM), we image the surface potential at the nanometer scale and quantitatively estimate the charges on these nanostructures as modulated by light. Both results are consistent with each other: the surface potential increases on switching on the light, and the photo-induced charges are around 15–25% and positive. A similar amount of the photo-induced charges in both P3HT islands and fibril is consistent with the π–π stacking nature of these nanostructures. As P3HT is a hole-conducting molecule, positive charges are found easily injected into a single island by a positively biased EFM tip, and then the injected charges are able to propagate all over the island.
- Published
- 2016
22. Hybrid nanogenerators based on triboelectrification of a dielectric composite made of lead-free ZnSnO 3 nanocubes
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Guo Wang, Haixia Xuan, Ruchuan Liu, Xi Chen, Yi Xi, and Lu Cheng
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Materials science ,Fabrication ,Polydimethylsiloxane ,Renewable Energy, Sustainability and the Environment ,Electrostatic force microscope ,Nanotechnology ,Dielectric ,Piezoelectricity ,chemistry.chemical_compound ,chemistry ,General Materials Science ,Electrical and Electronic Engineering ,Thin film ,Current density ,Triboelectric effect - Abstract
Based on mixed piezoelectric and ferroelectric nanostructures with polymers in various architectural forms, the flexible triboelectric nanogenerators (TENGs) have been extensively investigated. In this study, we design and fabricate lead-free ZnSnO 3 nanocubes @ polydimethylsiloxane (PDMS) based TENG by dispersing ZnSnO 3 nanocubes into PDMS elastomer at different ratios. Finally, the TENG can attain a maximum electrical output signal up to 400 V and 28 μA at a current density of 7 μA cm −2 , and an effective power to 3 mW at 6 wt% mass ZnSnO 3 mixed into PDMS. The harvested energy is utilized to drive 106 blue LEDs. In addition, this TENG generates stable electric power, even in the compressing-and-releasing process for over 500 cycles. Further investigation by electrostatic force microscopy shows clearly the maximum surface charge density appears at the optimal mixing ratio of ZnSnO 3 piezoelectric nanostructures into PDMS. This demonstrates that the optimization of the mixing ration between ZnSnO 3 piezoelectric nanostructures and PDMS is an effective method to increase the surface charges on the composite thin film and then improve the performance of the TENG. This TENG technology reveals a great candidate to be applied in large-scale device fabrications, flexible sensors and biological devices because of its easy fabrication process, high output power and biocompatibility.
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- 2015
23. Morphological quantification of proliferation-to-invasion transition in tumor spheroids
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Yang Jiao, Ruchuan Liu, Miaomiao Hai, Guo Chen, Yi He, Jianwei Shuai, Xixiang Zhang, Liyu Liu, Gao Wang, Ling Xiong, Yanping Liu, and Xuejuan Gao
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Cell ,Biophysics ,Breast Neoplasms ,02 engineering and technology ,Biochemistry ,Metastasis ,03 medical and health sciences ,Cell Line, Tumor ,Spheroids, Cellular ,Glioma ,medicine ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,U87 ,Lung cancer ,Molecular Biology ,Cell Proliferation ,Chemistry ,Spheroid ,Cancer ,Epithelial Cells ,021001 nanoscience & nanotechnology ,medicine.disease ,Primary tumor ,Extracellular Matrix ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,Female ,0210 nano-technology - Abstract
Background Metastasis determines the lethality of cancer. In most clinical cases, patients are able to live with tumor proliferation before metastasis. Thus, the transition from tumor proliferation to metastasis/invasion is essential. However, the mechanism is still unclear and especially, the proliferation-to-metastasis/invasion transition point has not been well defined. Therefore, quantitative characterization of this transition is urgently needed. Methods We have successfully developed a home-built living-cell incubation system combined with an inverted optical microscope, and a systematic, quantitative approach to describing the major characteristic morphological parameters for the identification of the critical transition points for tumor-cell spheroids in a collagen fiber scaffold. Results The system focuses on in vitro tumor modeling, e.g. the development of tumor-cell spheroids in a collagen fiber scaffold and the monitoring of cell transition from proliferation to invasion. By applying this approach to multiple tumor spheroid models, such as U87 (glioma tumor), H1299 (lung cancer), and MDA-MB-231 (breast cancer) cells, we have obtained quantitative morphological references to evaluate the proliferation-to-invasion transition time, as well as differentiating the invasion potential of tumor cells upon environmental changes, i.e. drug application. Conclusions Our quantitative approach provides a feasible clarification for the proliferation-to-invasion transition of in vitro tumor models (spheroids). Moreover, the transition time is a useful reference for the invasive potential of tumor cells. General significance This quantitative approach is potentially applicable to primary tumor cells, and thus has potential applications in the fields of cancer metastasis investigations and clinical diagnostics.
- Published
- 2020
24. Microfabrication-Based Three-Dimensional (3-D) Extracellular Matrix Microenvironments for Cancer and Other Diseases
- Author
-
Guo Chen, Zi-Rui Wang, Kena Song, Liyu Liu, and Ruchuan Liu
- Subjects
0301 basic medicine ,Angiogenesis ,extracellular matrix ,Drug Evaluation, Preclinical ,Review ,Computational biology ,Biology ,Catalysis ,Metastasis ,Inorganic Chemistry ,Extracellular matrix ,lcsh:Chemistry ,03 medical and health sciences ,Tumor Microenvironment ,medicine ,Humans ,cancer ,metastasis ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,microfabrication ,Tumor microenvironment ,Organic Chemistry ,Intravasation ,Cancer ,General Medicine ,medicine.disease ,Biomechanical Phenomena ,Computer Science Applications ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cancer cell ,Self-healing hydrogels ,Microtechnology - Abstract
Exploring the complicated development of tumors and metastases needs a deep understanding of the physical and biological interactions between cancer cells and their surrounding microenvironments. One of the major challenges is the ability to mimic the complex 3-D tissue microenvironment that particularly influences cell proliferation, migration, invasion, and apoptosis in relation to the extracellular matrix (ECM). Traditional cell culture is unable to create 3-D cell scaffolds resembling tissue complexity and functions, and, in the past, many efforts were made to realize the goal of obtaining cell clusters in hydrogels. However, the available methods still lack a precise control of cell external microenvironments. Recently, the rapid development of microfabrication techniques, such as 3-D printing, microfluidics, and photochemistry, has offered great advantages in reconstructing 3-D controllable cancer cell microenvironments in vitro. Consequently, various biofunctionalized hydrogels have become the ideal candidates to help the researchers acquire some new insights into various diseases. Our review will discuss some important studies and the latest progress regarding the above approaches for the production of 3-D ECM structures for cancer and other diseases. Especially, we will focus on new discoveries regarding the impact of the ECM on different aspects of cancer metastasis, e.g., collective invasion, enhanced intravasation by stress and aligned collagen fibers, angiogenesis regulation, as well as on drug screening.
- Published
- 2018
25. Realizations of highly heterogeneous collagen networks via stochastic reconstruction for micromechanical analysis of tumor cell invasion
- Author
-
Long Liang, Guo Chen, Hanqing Nan, Yang Jiao, Ruchuan Liu, and Liyu Liu
- Subjects
0301 basic medicine ,Matrigel ,Stochastic Processes ,Materials science ,Optimization problem ,Stochastic process ,Intravasation ,Models, Biological ,Biomechanical Phenomena ,Extracellular Matrix ,Extracellular matrix ,03 medical and health sciences ,030104 developmental biology ,Neoplasms ,Collagen network ,Simulated annealing ,Stochastic optimization ,Neoplasm Invasiveness ,Collagen ,Biological system ,Mechanical Phenomena - Abstract
Three-dimensional (3D) collective cell migration in a collagen-based extracellular matrix (ECM) is among one of the most significant topics in developmental biology, cancer progression, tissue regeneration, and immune response. Recent studies have suggested that collagen-fiber mediated force transmission in cellularized ECM plays an important role in stress homeostasis and regulation of collective cellular behaviors. Motivated by the recent in vitro observation that oriented collagen can significantly enhance the penetration of migrating breast cancer cells into dense Matrigel which mimics the intravasation process in vivo [Han et al. Proc. Natl. Acad. Sci. USA 113, 11208 (2016)PNASA60027-842410.1073/pnas.1610347113], we devise a procedure for generating realizations of highly heterogeneous 3D collagen networks with prescribed microstructural statistics via stochastic optimization. Specifically, a collagen network is represented via the graph (node-bond) model and the microstructural statistics considered include the cross-link (node) density, valence distribution, fiber (bond) length distribution, as well as fiber orientation distribution. An optimization problem is formulated in which the objective function is defined as the squared difference between a set of target microstructural statistics and the corresponding statistics for the simulated network. Simulated annealing is employed to solve the optimization problem by evolving an initial network via random perturbations to generate realizations of homogeneous networks with randomly oriented fibers, homogeneous networks with aligned fibers, heterogeneous networks with a continuous variation of fiber orientation along a prescribed direction, as well as a binary system containing a collagen region with aligned fibers and a dense Matrigel region with randomly oriented fibers. The generation and propagation of active forces in the simulated networks due to polarized contraction of an embedded ellipsoidal cell and a small group of cells are analyzed by considering a nonlinear fiber model incorporating strain hardening upon large stretching and buckling upon compression. Our analysis shows that oriented fibers can significantly enhance long-range force transmission in the network. Moreover, in the oriented-collagen-Matrigel system, the forces generated by a polarized cell in collagen can penetrate deeply into the Matrigel region. The stressed Matrigel fibers could provide contact guidance for the migrating cell cells, and thus enhance their penetration into Matrigel. This suggests a possible mechanism for the observed enhanced intravasation by oriented collagen.
- Published
- 2017
26. Unique synthesis of sandwiched graphene@(Li0.893Fe0.036)Co(PO4) nanoparticles as high-performance cathode materials for lithium-ion batteries
- Author
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Ling Fang, Huijuan Zhang, Li Liu, Xi Chen, Yu Wang, Yuanjuan Bai, and Ruchuan Liu
- Subjects
Materials science ,Renewable Energy, Sustainability and the Environment ,Graphene ,Doping ,Kinetics ,chemistry.chemical_element ,Nanoparticle ,Nanotechnology ,General Chemistry ,Cathode ,law.invention ,chemistry ,law ,Molecule ,General Materials Science ,Lithium ,Faraday efficiency - Abstract
In this report, a novel method towards synthesis of two-layer sandwiched graphene@(Li0.893Fe0.036)Co(PO4) nanoparticles (SG@LFCPO) has been presented. In the approach, the sheet-like precursor, as the sacrificial template, and glucose molecules, as the carbon source, are the key factors involved in forming the specific morphology in which both top and bottom graphene sheets tightly envelop the (Li0.893Fe0.036)Co(PO4) nanoparticles, just like a sandwich. Owing to the combination of various favorable conditions, such as Fe doping, graphene coating and morphology design, the as-prepared SG@LFCPO displays very promising performance in terms of rate performance (discharge capacity of 85 mA h g−1 at 20 C), cyclability (coulombic efficiency of around 92.6%), stability (capacity retention of 94.6% after 100 cycles) and fast kinetics.
- Published
- 2015
27. A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour-stroma interactions
- Author
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Jin-feng Chen, Ming Li, Ruchuan Liu, Xiaochen Wang, Liyu Liu, Fengrong Zhang, Yang Jiao, Wei Yuan, Zhong-Can Ou-Yang, Chunxiu Tian, Qihui Fan, Fangfu Ye, Wenwen Diao, Yue Yang, Xixiang Zhang, Haibo Han, and James D. Farrell
- Subjects
0301 basic medicine ,Stromal cell ,Biomedical Engineering ,Cell Culture Techniques ,Bioengineering ,Matrix metalloproteinase ,Biology ,Biochemistry ,Models, Biological ,Metastasis ,03 medical and health sciences ,Downregulation and upregulation ,In vivo ,Cell Line, Tumor ,medicine ,Tumor Microenvironment ,Humans ,Fluorescent Dyes ,chemistry.chemical_classification ,Biomolecule ,General Chemistry ,Equipment Design ,Microfluidic Analytical Techniques ,medicine.disease ,Cell biology ,Extracellular Matrix ,030104 developmental biology ,chemistry ,Cell culture ,Cancer cell ,Biomedical engineering - Abstract
A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tuneable biochemical gradients that mimics the tumour microenvironment of mammary glands was constructed for the investigation on the interactions between invasive breast cancer cells and stromal cells. The hollow microchambers in collagen provide a very similar 3-D environment to that in vivo that regulates collective cellular dynamics and behaviour, while the microfluidic channels surrounding the collagen microchamber arrays allow one to impose complex concentration gradients of specific biological molecules or drugs. We found that breast epithelial cells (MCF-10A) seeded in the microchambers formed lumen-like structures similar to those in epithelial layers. When MCF-10A cells were co-cultured with invasive breast cancer cells (MDA-MB-231), the formation of lumen-like structures in the microchambers was inhibited, indicating the capability of cancer cells to disrupt the structures formed by surrounding cells for further invasion and metastasis. Subsequent mechanism studies showed that down regulation of E-cad expression due to MMPs produced by the cancer cells plays a dominant role in determining the cellular behaviour. Our microfluidic system offers a robust platform for high throughput studies that aim to understand combinatorial effects of multiple biochemical and microenvironmental factors.
- Published
- 2017
28. Quantitative heterogeneity and subgroup classification based on motility of breast cancer cells*
- Author
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Liyu Liu, Ruchuan Liu, Yi He, Ling Xiong, Yanping Liu, Xixiang Zhang, Weijing Han, Gao Wang, Yang Jiao, Jianwei Shuai, Wei Yuan, and Junle Qu
- Subjects
Political science ,0103 physical sciences ,General Physics and Astronomy ,Library science ,Cancer metastasis ,02 engineering and technology ,Breast cancer cells ,021001 nanoscience & nanotechnology ,010306 general physics ,0210 nano-technology ,China ,01 natural sciences - Abstract
Cancer cell motility and its heterogeneity play an important role in metastasis, which is responsible for death of 90% of cancer patients. Here, in combination with a microfluidic technique, single-cell tracking, and systematic motility analysis, we present a rapid and quantitative approach to judge the motility heterogeneity of breast cancer cells MDA-MB-231 and MCF-7 in a well-defined three-dimensional (3D) microenvironment with controllable conditions. Following this approach, identification of highly mobile active cells in a medium with epithelial growth factor will provide a practical tool for cell invasion and metastasis investigation of multiple cancer cell types, including primary cells. Further, this approach could potentially become a speedy (∼hours) and efficient tool for basic and clinical diagnosis.
- Published
- 2019
29. A Nonencapsulative Pendulum‐Like Paper–Based Hybrid Nanogenerator for Energy Harvesting
- Author
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Hongmei Yang, Zhong Lin Wang, Ruchuan Liu, Wencong He, Mingming Deng, Qian Tang, Chenguo Hu, and Yi Xi
- Subjects
Materials science ,Renewable Energy, Sustainability and the Environment ,Pendulum ,Nanogenerator ,Mechanical engineering ,General Materials Science ,Paper based ,Energy harvesting - Published
- 2019
30. Remarkable disparity in mechanical response among the extracellular domains of type I and II cadherins
- Author
-
Fei Wu, Jean Paul Thiery, and Ruchuan Liu
- Subjects
Protein Conformation ,Cell adhesion molecule ,Cadherin ,Chemistry ,General Medicine ,Plasma protein binding ,Molecular Dynamics Simulation ,Cadherins ,Microscopy, Atomic Force ,Cell biology ,Molecular dynamics ,Protein structure ,Structural Biology ,Unfolded protein response ,Extracellular ,Calcium ,Protein Interaction Domains and Motifs ,Protein Multimerization ,Cell adhesion ,Molecular Biology ,Protein Binding ,Protein Unfolding - Abstract
Cadherins, a large family of calcium-dependent adhesion molecules, are critical for intercellular adhesion. While crystallographic structures for several cadherins show clear structural similarities, their relevant adhesive strengths vary and their mechanisms of adhesion between types I and II cadherin subfamilies are still unclear. Here, stretching of cadherins was explored experimentally by atomic force microscopy and computationally by steered molecular dynamics (SMD) simulations, where partial unfolding of the E-cadherin ectodomains was observed. The SMD simulations on strand-swapping cadherin dimers displayed similarity in binding strength, suggesting contributions of other mechanisms to explain the strength differences of cell adhesion in vivo. Systematic simulations on the unfolding of the extracellular domains of type I and II cadherins revealed diverse pathways. However, at the earliest stage, a remarkable similarity in unfolding was observed for the various type I cadherins that was distinct from that for type II cadherins. This likely correlates positively with their distinct adhesive properties, suggesting that the initial forced deformation in type I cadherins may be involved in cadherin-mediated adhesion. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:25
- Published
- 2013
31. Controlled generation of cell–laden hydrogel microspheres with core–shell scaffold mimicking microenvironment of tumor
- Author
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Yu Zhao, Yalei Lv, Guigen Zhang, Yi He, Guo Chen, Miaomiao Hai, Yuenan Li, Ruchuan Liu, and Liyu Liu
- Subjects
0301 basic medicine ,Matrigel ,Scaffold ,Materials science ,Multiphysics ,Microfluidics ,Multiphase flow ,General Physics and Astronomy ,02 engineering and technology ,021001 nanoscience & nanotechnology ,03 medical and health sciences ,chemistry.chemical_compound ,3D cell culture ,030104 developmental biology ,chemistry ,Self-healing hydrogels ,Biophysics ,Propidium iodide ,0210 nano-technology - Abstract
Development of an in vitro three-dimensional (3D) model that closely mimics actual environment of tissue has become extraordinarily important for anti-cancer study. In recent years, various 3D cell culture systems have been developed, with multicellular tumor spheroids being the most popular and effective model. In this work, we present a microfluidic device used as a robust platform for generating core–shell hydrogel microspheres with precisely controlled sizes and varied components of hydrogel matrix. To gain a better understanding of the governing mechanism of microsphere formation, computational models based on multiphase flow were developed to numerically model the droplet generation and velocity field evolution process with COMSOL Multiphysics software. Our modeling results show good agreement with experiments in size dependence on flow rate as well as effect of vortex flow on microsphere formation. With real-time tuning of the flow rates of aqueous phase and oil phase, tumor cells were encapsulated into the microspheres with controllable core–shell structure and different volume ratios of core (comprised of alginate, Matrigel, and/or Collagen) and shell (comprised of alginate). Viability of cells in four different hydrogel matrices were evaluated by standard acridine orange (AO) and propidium iodide (PI) staining. The proposed microfluidic system can play an important role in engineering the in vitro micro-environment of tumor spheroids to better mimic the actual in vivo 3D spatial structure of a tumor and perfect the 3D tumor models for more effective clinical therapies.
- Published
- 2018
32. Modeling three-dimensional invasive solid tumor growth in heterogeneous microenvironment under chemotherapy
- Author
-
Miaomiao Hai, Jianwei Shuai, Jiaen Yang, Qihui Fan, Zhijian Hu, Liyu Liu, Hang Xie, Guo Chen, Yang Jiao, Ruchuan Liu, and Yue Yang
- Subjects
0301 basic medicine ,medicine.medical_treatment ,Cancer Treatment ,lcsh:Medicine ,0302 clinical medicine ,Neoplasms ,Medicine and Health Sciences ,Tumor Microenvironment ,Cell Cycle and Cell Division ,Tissues and Organs (q-bio.TO) ,lcsh:Science ,Solid tumor ,Drug Distribution ,Mass Diffusivity ,Multidisciplinary ,Invasive Tumors ,Pharmaceutics ,Chemistry ,Physics ,Chemical Reactions ,Primary tumor ,Oncology ,Cell Processes ,030220 oncology & carcinogenesis ,Physical Sciences ,Hybrid model ,Research Article ,Clinical Oncology ,In silico ,Antineoplastic Agents ,Cellular level ,Models, Biological ,Cancer Chemotherapy ,03 medical and health sciences ,Drug Therapy ,medicine ,Chemotherapy ,Humans ,Pharmacokinetics ,Neoplasm Invasiveness ,Tumor growth ,Quantitative Biology - Populations and Evolution ,Cell Proliferation ,Pharmacology ,Decomposition ,Chemical Physics ,lcsh:R ,Populations and Evolution (q-bio.PE) ,Cancers and Neoplasms ,Biology and Life Sciences ,Quantitative Biology - Tissues and Organs ,Cell Biology ,medicine.disease ,030104 developmental biology ,Drug concentration ,FOS: Biological sciences ,Cancer research ,lcsh:Q ,Clinical Medicine - Abstract
A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations reproduce the well-established observation that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization., Comment: 41 pages, 8 figures
- Published
- 2018
33. The Impact of Hybrid Compositional Film/Structure on Organic–Inorganic Perovskite Solar Cells
- Author
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Wei Chen, Guo Chen, Zhubing He, Yinghui Wu, Liyu Liu, and Ruchuan Liu
- Subjects
bulk heterojunctions ,Materials science ,polymer ,General Chemical Engineering ,Energy conversion efficiency ,Nanotechnology ,Review ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,perovskite solar cells ,01 natural sciences ,0104 chemical sciences ,Layered structure ,Film structure ,Organic inorganic ,composite-structured ,General Materials Science ,2 dimensional ,0210 nano-technology ,Cs-based perovskite ,layered structure ,Perovskite (structure) - Abstract
Perovskite solar cells (PSCs) have been intensively investigated over the last several years. Unprecedented progress has been made in improving their power conversion efficiency; however, the stability of perovskite materials and devices remains a major obstacle for the future commercialization of PSCs. In this review, recent progress in PSCs is summarized in terms of the hybridization of compositions and device architectures for PSCs, with special attention paid to device stability. A brief history of the development of PSCs is given, and their chemical structures, optoelectronic properties, and the different types of device architectures are discussed. Then, perovskite composition engineering is reviewed in detail, with particular emphasis on the cationic components and their impact on film morphology, the optoelectronic properties, device performance, and stability. In addition, the impact of two-dimensional and/or one-dimensional and nanostructured perovskites on structural and device stability is surveyed. Finally, a future outlook is proposed for potential resolutions to overcome the current issues.
- Published
- 2018
34. SKPM study on organic-inorganic perovskite materials
- Author
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Yinghui Wu, Guo Chen, Ruchuan Liu, Yi He, Kena Song, Liyu Liu, and Xi Chen
- Subjects
Materials science ,Fermi level ,General Physics and Astronomy ,Halide ,chemistry.chemical_element ,02 engineering and technology ,Substrate (electronics) ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,lcsh:QC1-999 ,0104 chemical sciences ,symbols.namesake ,Scanning probe microscopy ,chemistry ,Chemical physics ,symbols ,Chlorine ,Particle ,Work function ,0210 nano-technology ,lcsh:Physics ,Perovskite (structure) - Abstract
We report Atomic Force Microscopy (AFM) and Scanning Kelvin Probe Microscopy (SKPM) studies on the surface morphology and surface potential properties of CH3NH3PbI3, CH3NH3PbI3-xClx, CH3NH3PbI3-xBrx and CH3NH3PbBr3-xClx, respectively. For CH3NH3PbI3 rod structure, its surface potential is independent of the precursor concentration, suggesting a robust electronic feature. Surface potential studies of CH3NH3PbI3 particle reveal that the Fermi level within CH3NH3PbI3 is strongly influenced by the substrate. In the case of CH3NH3PbI3-xClx, its surface potential depends on precursor concentrations and we suspect that chlorine concentrated solutions might lead to more chlorine incorporation in the final products, thus lowering its Fermi level. Also, we studied the surface potentials of CH3NH3PbI3-xBrx and CH3NH3PbBr3-xClxwith specified halide ratios. The surface potential differences between different samples are related to their work function variations. These results are helpful to the understanding of the structural and electronic properties of perovskite materials.
- Published
- 2018
35. Revealing two-state protein-protein interactions of calmodulin by single-molecule spectroscopy
- Author
-
Ruchuan Liu, Xin Tan, Lu, H. Peter, and Dehong Hu
- Subjects
Calmodulin -- Electric properties ,Nitrogen compounds -- Electric properties ,Energy transformation -- Analysis ,Chemistry - Abstract
A single-molecule fluorescence resonance energy transfer (FRET) and polarization study of conformational dynamics of calmodulin (CaM) interacting with a target peptide, C28W of a 28 amino acid oligomer, is reported. The binding-unbinding motions of the N-terminal domain of the CaM in CaM/C28W complexes have revealed strong evidence of a two-state binding interaction of CaM-mediated cell signaling.
- Published
- 2006
36. Enhancing the performance of NaNbO3triboelectric nanogenerators by dielectric modulation and electronegative modification
- Author
-
Ruchuan Liu, Qipeng Liu, Hengyu Guo, Chengguo Hu, Yinghui Wu, Yi Xi, Lu Cheng, Bolun Du, Meihui Lai, and Guanlin Liu
- Subjects
Fabrication ,Materials science ,Acoustics and Ultrasonics ,Polydimethylsiloxane ,business.industry ,Nanogenerator ,02 engineering and technology ,Dielectric ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Piezoelectricity ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry.chemical_compound ,chemistry ,Optoelectronics ,0210 nano-technology ,business ,Triboelectric effect ,Power density ,Diode - Abstract
Increasing the triboelectric charge density on the friction layer of polydimethylsiloxane (PDMS) is a basic approach towards improving the output performance of a triboelectric nanogenerator (TENG). Most previous work focuses on the surface structure or dielectric properties, nonetheless, a few studies have focused on electronegative modification. NaNbO3-PDMS TENG (N-TENG) devices are fabricated by dispersing cubic NaNbO3, which is a lead-free piezoelectric material with molecular oxygen dangling bonds on the surface of the crystal, into the PDMS at different mass ratios. When the mass ratio is 7 wt%, the maximum output performance of the N-TENG is obtained. The open-circuit voltage is 550 V, the short-circuit current is 16 µA, and the effective power densities reach up to 5.5 W m−2 at a load resistance of ~100 MΩ. The N-TENG has been used to assemble self-powered electronic watches and illuminate commercial light-emitting diodes, respectively. Its fundamental mechanism has also been discussed in detail from the perspective of dielectric modulation and electronegative modification. This N-TENG technology is revealed to be a splendid candidate for application in large-scale device fabrication, flexible sensors and biological devices thanks to its easy fabrication process, low consumption, high output power density and biocompatibility.
- Published
- 2017
37. Imaging of Photoinduced Interfacial Charge Separation in Conjugated Polymer/Semiconductor Nanocomposites
- Author
-
Ruchuan Liu
- Subjects
Conductive polymer ,Nanocomposite ,Nanostructure ,Materials science ,business.industry ,Energy conversion efficiency ,Nanotechnology ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,General Energy ,Semiconductor ,Photoinduced charge separation ,law ,Microscopy ,Solar cell ,Physical and Theoretical Chemistry ,business - Abstract
Though having attracted extensive interests as the substitution for dye-sensitized TiO2 solar cell, hybrid nanocomposites of conducting polymer, and inorganic semiconductors for solar cells have still gave much less conversion efficiency. The photovoltaic processes are expected to take place mainly near the heterogeneous interfaces but directly visualizing those processes and correlating them with local nanostructures have not been established yet. Such a relationship is very important for the improvement of structural designs of the hybrid systems with better conversion efficiencies. In this article, two advanced microscopic techniques, near-field scanning optical microscopy, and scanning electrostatic potential microscopy are employed to explore the photoinduced charge separation processes and kinetics in nanocomposites of poly(1,4-phenylenevinylene) and TiO2 nanoparticles, as well as their association with the local nanostructures. The results suggest that charge separation can be the dominant pathway ...
- Published
- 2009
38. Studying and switching electron transfer: From the ensemble to the single molecule
- Author
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Holman, Michael W., Ruchuan Liu, Ling Zang, Ping Yan, DiBenedetto, Sara A., Bowers, Robert D., and Adams, David M.
- Subjects
Electron transport -- Spectra ,Molecular structure -- Research ,Chemistry - Abstract
A report is presented on the systematic investigation of photoinduced intramolecular electron transfer (IET) in a series of donor-bridge-acceptor molecules as a means of understanding electron transport through the bridge. In addition, ab initio quantum chemical methods were used to calculate the through-space component of the electronic coupling matrix element.
- Published
- 2004
39. Fluctuating Two-State Light Harvesting in a Photosynthetic Membrane
- Author
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Ruchuan Liu, H. Peter Lu, Dehong Hu, Duohai Pan, Xiaohua Zeng, and Samuel Kaplan
- Subjects
Chemistry ,Energy transfer ,Photosynthesis ,Photochemistry ,Fluorescence spectroscopy ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Light-harvesting complex ,Chemical energy ,General Energy ,Chemical physics ,Microscopic imaging ,Photosynthetic membrane ,Physical and Theoretical Chemistry - Abstract
The mechanism by which light is converted into chemical energy in a natural photosynthetic system has drawn considerable research interest. Using fluorescence spectroscopy and microscopic imaging, ...
- Published
- 2007
40. Homophilic interaction and deformation of E-cadherin and cadherin 7 probed by single molecule force spectroscopy
- Author
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Fei Wu, Chen Lu, Chwee Teck Lim, Jean Paul Thiery, Wu Qiu, Ahmed El Marjou, Prashant Kumar, and Ruchuan Liu
- Subjects
Magnetic tweezers ,Total internal reflection fluorescence microscope ,Cadherin ,Chemistry ,Biophysics ,Force spectroscopy ,Plasma protein binding ,Adhesion ,Cadherins ,Microscopy, Atomic Force ,Biochemistry ,Cell biology ,Protein Structure, Tertiary ,Magnetics ,Unfolded protein response ,Cell Adhesion ,Cell adhesion ,Molecular Biology ,Mechanical Phenomena ,Protein Binding ,Protein Unfolding - Abstract
Cadherin-mediated adhesion plays a crucial role in multicellular organisms. Dysfunction within this adhesion system has major consequences in many pathologies, including cancer invasion and metastasis. However, mechanisms controlling cadherin recognition and adhesive strengthening are only partially understood. Here, we investigated the homophilic interactions and mechanical stability of the extracellular (EC) domains of E-cadherin and cadherin 7 using atomic force microscopy and magnetic tweezers. Besides exhibiting stronger interactions, E-cadherin also showed more efficient force-induced self-strengthening of interactions than cadherin 7. In addition, the distributions of the unbinding forces for both cadherins partially overlap with those of the unfolding forces, indicating that partial unfolding/deformation of the cadherin EC domains may take place during their homophilic interactions. These conformational changes may be involved in cadherins physiology function and contribute to the significant differences in adhesive strength mediated by type I and type II cadherins.
- Published
- 2015
41. Correction: Corrigendum: Force-dependent conformational switch of α-catenin controls vinculin binding
- Author
-
Peiwen Cong, Benoit Ladoux, Jie Yan, Artem K. Efremov, Rima Seddiki, Mingxi Yao, Chwee Teck Lim, Ruchuan Liu, Wu Qiu, Manon Payre, and René-Marc Mège
- Subjects
α catenin ,Mechanobiology ,Multidisciplinary ,Chemistry ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,Vinculin binding - Abstract
Nature Communications 5: Article number: 4525 (2014); Published: 31 July 2014; Updated: 4 March 2015 The affiliation details for Jie Yan are incorrect in this Article. The correct affiliation details for this author are given below: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
- Published
- 2015
42. Biomechanics of Collective Cell Migration in Cancer Progression: Experimental and Computational Methods.
- Author
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Catalina-Paula Spatarelu, Hao Zhang, Nguyen, Dung Trung, Xinyue Han, Ruchuan Liu, Guo, Qiaohang, Notbohm, Jacob, Fan, Jing, Liyu Liu, and Zi Chen
- Published
- 2019
- Full Text
- View/download PDF
43. A single molecule probe based on intermolecular electron transfer
- Author
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Ling Zang, Ruchuan Liu, Holman, Micheal W., Nguyen, Kim T., and Adams, David M.
- Subjects
Chromophores -- Research ,Electron transport -- Research ,Chemistry - Abstract
Single molecules level represents the ultimate degree of sensitivity for sensing and imaging and molecules composed of a fluorescent chromophore a binding site, and a mechanism of communication between the two are used in chemosensory and biological applications. It is concluded that the SMS of a new molecular probe uses intermolecular electron transfer mechanism to detect binding.
- Published
- 2002
44. A conformational switch of intramolecular electron transfer
- Author
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David M. Adams, Fady I. Ishak, Koon-Cheung Ching, Ping Yan, Ruchuan Liu, and Michael W. Holman
- Subjects
Chemistry ,General Physics and Astronomy ,Dihedral angle ,Gibbs free energy ,Specific orbital energy ,symbols.namesake ,Electron transfer ,Chemical physics ,Non-bonding orbital ,Computational chemistry ,Intramolecular force ,symbols ,Moiety ,Density functional theory ,sense organs ,Physical and Theoretical Chemistry ,skin and connective tissue diseases - Abstract
Quantum chemical calculations and experiments on model compounds are used to study the effect of conformational changes on intramolecular electron transfer in perylenebisimide–biphenyl dyads. The molecular orbital energy level of the biphenyl moiety and thus the free energy change for electron transfer depends on the dihedral angle between the two phenyl rings. Dramatic changes in the orbital energy levels result in very different electron transfer behavior for three model compounds. These changes are accurately predicted by calculations using density functional theory, which also give accurate results for geometries, suggesting such calculations can be useful in designing molecular electronic species.
- Published
- 2005
45. Single-Molecule Spectroscopy of Interfacial Electron Transfer
- Author
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Ruchuan Liu, David M. Adams, and Michael W. Holman
- Subjects
business.industry ,Molecular electronics ,General Chemistry ,Electron ,Chromophore ,Biochemistry ,Molecular physics ,Electron spectroscopy ,Catalysis ,chemistry.chemical_compound ,Electron transfer ,Colloid and Surface Chemistry ,Semiconductor ,chemistry ,Atomic physics ,Spectroscopy ,business ,Perylene - Abstract
It is widely appreciated that single-molecule spectroscopy (SMS) can be used to measure properties of individual molecules which would normally be obscured in an ensemble-averaged measurement. In this report we show how SMS can be used to measure photoinduced interfacial electron transfer (IET) and back electron transfer rates in a prototypical chromophore-bridge-electrode nonadiabatic electron transfer system. N-(1-hexylheptyl)-N'-(12-carboxylicdodecyl)perylene-3,4,9,10-tetracarboxylbisimide was synthesized and incorporated into mixed self-assembled monolayers (SAMs) on an ITO (tin-doped indium oxide, a p-type semiconductor) electrode. Single-molecule fluorescence time trajectories from this system reveals "blinks", momentary losses in fluorescence (>20 ms to seconds in duration), which are attributed to discrete electron transfer events: electron injection from the perylene chromophore into the conduction band of the ITO leads to the loss of fluorescence, and charge recombination (back electron transfer) leads to the return of fluorescence. Such blinks are not observed when an electrode is not present. The fluorescence trajectories were analyzed to obtain the forward and back electron rates; the measured rates are found to lie in the millisecond to second regime. Different rates are observed for different molecules, but the lifetime distributions for the forward or back electron transfer for any given molecule are well fit by single exponential kinetics. The methodology used is applicable to a wide variety of systems and can be used to study the effects of distance, orientation, linker, environment, etc. on electron transfer rates. The results and methodology have implications for molecular electronics, where understanding and controlling the range of possible behaviors inherent to molecular systems will likely be as important as understanding the individual behavior of any given molecule.
- Published
- 2003
46. Single-Molecule Spectroscopy of Intramolecular Electron Transfer in Donor-Bridge-Acceptor Systems
- Author
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Michael W. Holman, David M. Adams, Ruchuan Liu, and Ling Zang
- Subjects
chemistry.chemical_compound ,Electron transfer ,Chemistry ,Chemical physics ,Intramolecular force ,Molecule ,Physical and Theoretical Chemistry ,Chromophore ,Photochemistry ,Spectroscopy ,Acceptor ,Fluorescence ,Perylene - Abstract
It is widely appreciated that single-molecule spectroscopy (SMS) can be used to measure properties of individual molecules which would normally be obscured in an ensemble-averaged measurement. In this article, we show how SMS can be used to investigate intramolecular electron transfer (IET) processes in model dimer systems composed of two perylene chromophores connected via an adjustable bridge. The fluorescence behaviors of a large number of molecules are cataloged and the results statistically analyzed to gauge information about the range of behaviors of the ensemble. Single-molecule fluorescence time trajectories reveal “blinks”, momentary losses in fluorescence (>20 ms to seconds in duration), which are attributed to discrete IET excursions to the charge-separated (CS) state. We find that fluorescence blinking behavior is dependent on bridge length and chromophore geometry, which affect the electronic coupling and therefore the IET. The statistical trends observed in this analysis are used to corrobor...
- Published
- 2003
47. Ultraviolet Photoluminescence from 4H–SiC Nanocrystalline Films Deposited on Silicon Substrate
- Author
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Ruchuan Liu, Yaozhong Ruan, Beifang Yan, and Zhengping Fu
- Subjects
Materials science ,Photoluminescence ,Silicon ,business.industry ,Band gap ,Mechanical Engineering ,Nanocrystalline silicon ,chemistry.chemical_element ,Substrate (electronics) ,Condensed Matter Physics ,Nanocrystalline material ,Chemical engineering ,chemistry ,Mechanics of Materials ,Optoelectronics ,General Materials Science ,business ,Luminescence ,Silicon oxide - Abstract
Preferred-orientated 4H–SiC nanocrystalline films on silicon substrates were successfully prepared by the pyrolysis of the polyimide Langmuir–Blodgett films containing nanometer-sized amorphous silicon nitride powders. Fourier-transform infrared spectra revealed 4H–SiC nanoparticles with interfacial silicon oxide. Ultraviolet photoluminescence with energies above the band gap of bulk 4H–SiC was observed from the films in which the mean size of 4H–SiC particles was 10 nm, while no photoluminescence was observed from the films in which the mean size of particles was 17 nm. A quantum confinement/luminescence center model is suggested to explain the origin of the ultraviolet luminescence.
- Published
- 2002
48. Plasmon-driven surface catalysis in hybridized plasmonic gap modes
- Author
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Mengtao Sun, Ruchuan Liu, Ting Liu, Yurui Fang, Yingzhou Huang, Hui Wang, Weijia Wen, and Shuxia Wang
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Multidisciplinary ,Materials science ,business.industry ,Surface plasmon ,Nanoparticle ,Physics::Optics ,Bioinformatics ,Method of image charges ,Article ,symbols.namesake ,Electric field ,Nano ,symbols ,Optoelectronics ,Raman spectroscopy ,business ,Raman scattering ,Plasmon - Abstract
Plasmon-driven surface catalytic (PDSC) reaction in Ag/Au nanoparticle monomer or dimer-film gaps are experimentally and theoretically investigated, using surface enhanced Raman scattering (SERS) and finite element method. The variation of SERS spectra in different nano gaps of nanoparticle-film systems indicated the PDSC reaction was largely depended on the number of nanoparticles. The higher Raman intensity of p, p'-dimercaptoazobenzene (DMAB) in dimer-film nanogap was because effective coupling of induced image charge on metal film in hybridized plasmonic gap mode, which was confirmed by the electric field distribution. Furthermore, the influence of material and wavelength was also studied to obtain the optimal experimental condition for best surface catalysis in hybridized plasmonic gap mode. Our studies in this common configuration of plasmonic nanostructure are of great significance not only in the field of catalysis on metal surface but also in other surface plasmon fields such as senor, photon detection, water splitting, etc.
- Published
- 2014
49. Biophysical Properties of Intrinsically Disordered p130Cas Substrate Domain — Implication in Mechanosensing
- Author
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Fei Wu, Soumya Ranganathan, Hiroaki Machiyama, Ruchuan Liu, Neelesh Soni, Mallur S. Madhusudhan, Yasuhiro Sawada, Takashi Ohe, Hiroaki Hirata, Rong Gao, Christopher W. V. Hogue, and Kinya Hotta
- Subjects
Circular dichroism ,Globular protein ,Protein domain ,Biophysics ,Intrinsically disordered proteins ,Microscopy, Atomic Force ,Mechanotransduction, Cellular ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Molecular Cell Biology ,Genetics ,lcsh:QH301-705.5 ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,LIM domain ,Polyproline helix ,Protein Unfolding ,chemistry.chemical_classification ,0303 health sciences ,Ecology ,030302 biochemistry & molecular biology ,Biology and Life Sciences ,Computational Biology ,Tyrosine phosphorylation ,Cell Biology ,Intrinsically Disordered Proteins ,Crk-Associated Substrate Protein ,lcsh:Biology (General) ,Computational Theory and Mathematics ,Biochemistry ,chemistry ,Modeling and Simulation ,Radius of gyration ,Research Article - Abstract
Mechanical stretch-induced tyrosine phosphorylation in the proline-rich 306-residue substrate domain (CasSD) of p130Cas (or BCAR1) has eluded an experimentally validated structural understanding. Cellular p130Cas tyrosine phosphorylation is shown to function in areas without internal actomyosin contractility, sensing force at the leading edge of cell migration. Circular dichroism shows CasSD is intrinsically disordered with dominant polyproline type II conformations. Strongly conserved in placental mammals, the proline-rich sequence exhibits a pseudo-repeat unit with variation hotspots 2–9 residues before substrate tyrosine residues. Atomic-force microscopy pulling experiments show CasSD requires minimal extension force and exhibits infrequent, random regions of weak stability. Proteolysis, light scattering and ultracentrifugation results show that a monomeric intrinsically disordered form persists for CasSD in solution with an expanded hydrodynamic radius. All-atom 3D conformer sampling with the TraDES package yields ensembles in agreement with experiment when coil-biased sampling is used, matching the experimental radius of gyration. Increasing β-sampling propensities increases the number of prolate conformers. Combining the results, we conclude that CasSD has no stable compact structure and is unlikely to efficiently autoinhibit phosphorylation. Taking into consideration the structural propensity of CasSD and the fact that it is known to bind to LIM domains, we propose a model of how CasSD and LIM domain family of transcription factor proteins may function together to regulate phosphorylation of CasSD and effect machanosensing., Author Summary Mechanical stretching of cells causes the substrate domain of p130Cas (CasSD) to be phosphorylated on 15 tyrosine residues embedded along its length. CasSD is rich in proline and surprisingly well conserved in placental mammals. Stretching of CasSD by atomic force microscopy has identified that it requires far less force than normal folded proteins. Classical biophysical analyses have determined that CasSD is a typical intrinsically disordered protein, a difficult-to-study group of molecules covering about 30% of human proteins. The average size of CasSD is larger and elongated than folded globular proteins but smaller than chemically denatured proteins. We have simulated a large number of all-atom protein structures using a fast all-atom sampling method. The result is in good agreement with the experimental observation. As it is already known that stretching somehow exposes the tyrosine residues to phosphorylation, a mechanism is proposed where straightening of the p130Cas substrate domain backbone conformation through mechanical stretching can lead to dissociation of p130Cas-binding LIM domain proteins and exposure of CasSD tyrosine residues for phosphorylation. This study has led to a new model of a protein-based mechanism of force sensing at the leading edge of cells that allows the cells to feel their way as they move.
- Published
- 2014
50. Force-dependent conformational switch of α-catenin controls vinculin binding
- Author
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Peiwen Cong, Ruchuan Liu, Chwee Teck Lim, Mingxi Yao, Wu Qiu, Benoit Ladoux, Jie Yan, Rima Seddiki, René-Marc Mège, Artem K. Efremov, and Manon Payre
- Subjects
Magnetic tweezers ,animal structures ,Optical Tweezers ,Recombinant Fusion Proteins ,General Physics and Astronomy ,macromolecular substances ,Plasma protein binding ,Mechanotransduction, Cellular ,General Biochemistry, Genetics and Molecular Biology ,Protein Structure, Secondary ,Mice ,Protein structure ,Animals ,Mechanotransduction ,Binding site ,Vinculin binding ,Multidisciplinary ,Binding Sites ,biology ,Chemistry ,General Chemistry ,Adhesion ,Vinculin ,musculoskeletal system ,Cell biology ,Protein Structure, Tertiary ,Actin Cytoskeleton ,Magnetic Fields ,Gene Expression Regulation ,biology.protein ,Stress, Mechanical ,alpha Catenin ,Protein Binding - Abstract
Force sensing at cadherin-mediated adhesions is critical for their proper function. α-Catenin, which links cadherins to actomyosin, has a crucial role in this mechanosensing process. It has been hypothesized that force promotes vinculin binding, although this has never been demonstrated. X-ray structure further suggests that α-catenin adopts a stable auto-inhibitory conformation that makes the vinculin-binding site inaccessible. Here, by stretching single α-catenin molecules using magnetic tweezers, we show that the subdomains MI vinculin-binding domain (VBD) to MIII unfold in three characteristic steps: a reversible step at ~5 pN and two non-equilibrium steps at 10-15 pN. 5 pN unfolding forces trigger vinculin binding to the MI domain in a 1:1 ratio with nanomolar affinity, preventing MI domain refolding after force is released. Our findings demonstrate that physiologically relevant forces reversibly unfurl α-catenin, activating vinculin binding, which then stabilizes α-catenin in its open conformation, transforming force into a sustainable biochemical signal.
- Published
- 2014
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