Search

Protein coating material is important in many technological fields. The interaction between carbon nanomaterial and protein is especially interesting since it makes the development of novel hybrid materials possible. Functional Bacterial Amyloid (FuBA) is promising as a coating material because of its desirable features such as well-defined molecular structure, robustness against harsh conditions, and easily engineerable functionality. Here, we report the systematic assembly of the functional amyloid protein, CsgA from Escherichia coli (E. coli) on graphite. We characterize the assemblies using Scanning Tunnelling Microscopy (STM) and show that CsgA forms assemblies according to systematic patterns, dictated by the graphite lattice. In addition, we show that graphite flakes induce the fibrillization of CsgA, in vitro, suggesting a surface-induced conformational change of CsgA facilitated by the graphite lattice. Using coarse-grained molecular dynamics simulations, we model the adhesion and lamellar formation of a CsgA-derived peptide and conclude that peptides are adsorbed both as monomers and smaller aggregates leading initially to unordered graphite-bound aggregates which are followed by rearrangement into lamellar structures. Finally, we show that CsgA-derived peptides can be immobilized in very systematic assemblies and their molecular orientation can be tuned using a small chaperone-like molecule. Our findings have implications for the development of FuBA-based biosensors, catalysts, and other technologies requiring well-defined protein assemblies on graphite.

The emergence of exquisitely organized axonal projections is one of the greatest wonders of nervous system development. In addition to growing along stereotyped directions, axons join one another as they extend. It is well known that axonal growth cones recognize cell surface guidance cues on axons and either grow along the axons or away from the axons. However, it is less well understood whether and how the growth cones communicate with each other and, if so, what do these interactions mean. Recent studies from our lab provided direct evidence that the growth cones do interact with each other during axon pathfinding. And this interaction is regulated by highly regulated protein-protein interactions among components of the planar cell polarity pathway. The disruption of these interactions lead to guidance defects and disorganization of axons. We propose that this local inter-growth cone PCP-like signaling mechanism reinforces and increases the sensitivity of the growth cone response to shallow Wnt gradients to turn in a precise and organized fashion.

In order to solve the problem of improving the effectiveness of muscle strength training for sprinters, this paper presents a study using image observation technology. The main content of this technology research is to determine the experimental object and method according to the image observation and muscle characteristics. Through the data processing and other processes, it is concluded that the image observation technology has a high accuracy in the observation of muscle movement patterns. The experimental results show that when the relationship number r = 0.99 , the average error of prediction is 0.09, and the image observation technology has a high accuracy in the observation of muscle movement. Conclusion. It is proved that the technical research of image observation is effective and accurate for improving the training of sports muscle strength of sprinters.

At least two-thirds of spinal cord injury cases are anatomically incomplete, without complete spinal cord transection, although the initial injuries cause complete loss of sensory and motor functions. The malleability of neural circuits and networks allows varied extend of functional restoration in some individuals after successful rehabilitative training. However, in most cases, the efficiency and extent are both limited and uncertain, largely due to the many obstacles of repair. The restoration of function after anatomically incomplete injury is in part made possible by the growth of new axons or new axon branches through the spared spinal cord tissue and the new synaptic connections they make, either along the areas they grow through or in the areas they terminate. This review will discuss new progress on the understanding of the role of axon guidance molecules, particularly the Wnt family proteins, in spinal cord injury and how the knowledge and tools of axon guidance can be applied to increase the potential of recovery. These strategies, combined with others, such as neuroprotection and rehabilitation, may bring new promises. The recovery strategies for anatomically incomplete spinal cord injuries are relevant and may be applicable to traumatic brain injury and stroke.

Directional and positional information is essential for the diverse neuronal morphology and connectivity during development. The direction of axon growth is critical for building the correct networks among neurons, sometimes from far away. Neuronal synapses are asymmetric cell-cell junctions with distinct presynaptic and postsynaptic structures to convey neural activity in a directional fashion. Recent studies show that some of the key asymmetry is mediated by highly conversed cell polarity signaling pathways. These pathways, planar cell polarity and apical-basal polarity, are not required for the global axon-dendrite polarity. Therefore, the apparent distinct types of morphological asymmetry in the nervous system, growth cone turning and synaptic junctions, are mediated by similar cell polarity signaling mechanisms widely used in cellular and tissue morphogenesis.

Significance In addition to responding to directional cues, axons join one another as they extend to form highly organized projections. We show here that growth cones communicate with each other, and this communication is mediated by planar cell polarity signaling components, which are known to mediate cell–cell interactions in tissue polarization. This interaction is, in part, mediated by an intercellular interaction between Frizzled3 and Vangl2. Leucine-rich repeat kinase 2 (LRRK2), encoded by a Parkinson’s disease gene, regulates Frizzled3 phosphorylation and the intercellular interaction between Frizzled3 and Vangl2. Both loss-of-function and gain-of-function LRRK2 mutants show axon guidance defects, including those of the dopaminergic neurons, suggesting that this Parkinson’s disease gene plays important roles in growth cone–growth cone interactions during axon development., Axon–axon interactions are essential for axon guidance during nervous system wiring. However, it is unknown whether and how the growth cones communicate with each other while sensing and responding to guidance cues. We found that the Parkinson’s disease gene, leucine-rich repeat kinase 2 (LRRK2), has an unexpected role in growth cone–growth cone communication. The LRRK2 protein acts as a scaffold and induces Frizzled3 hyperphosphorylation indirectly by recruiting other kinases and also directly phosphorylates Frizzled3 on threonine 598 (T598). In LRRK1 or LRRK2 single knockout, LRRK1/2 double knockout, and LRRK2 G2019S knockin, the postcrossing spinal cord commissural axons are disorganized and showed anterior–posterior guidance errors after midline crossing. Growth cones from either LRRK2 knockout or G2019S knockin mice showed altered interactions, suggesting impaired communication. Intercellular interaction between Frizzled3 and Vangl2 is essential for planar cell polarity signaling. We show here that this interaction is regulated by phosphorylation of Frizzled3 at T598 and can be regulated by LRRK2 in a kinase activity-dependent way. In the LRRK1/2 double knockout or LRRK2 G2019S knockin, the dopaminergic axon bundle in the midbrain was significantly widened and appeared disorganized, showing aberrant posterior-directed growth. Our findings demonstrate that LRRK2 regulates growth cone–growth cone communication in axon guidance and that both loss-of-function mutation and a gain-of-function mutation (G2019S) cause axon guidance defects in development.

The Planar cell polarity (PCP) pathway is known to mediate the function of the Wnt proteins in growth cone guidance. Here, we show that the PCP pathway may directly influence local protein synthesis within the growth cones. We found that Fragile X Messenger Ribonucleoprotein 1 (FMRP) interacts with Fzd3. This interaction is negatively regulated by Wnt5a, which induces FMRP phosphorylation. Knocking down FMRP via electroporating shRNAs into the dorsal spinal cord lead to a randomization of anterior-posterior turning of post-crossing commissural axons, which could be rescued by a FMRP rescue construct. Using RNAscope, we found that some of the FMRP target mRNAs encoding PCP components, PRICKLE2 and Celsr2, as well as regulators of cytoskeletal dynamics and components of cytoskeleton, APC, Cfl1, Map1b, Tubb3 and Actb, are present in the commissural neuron growth cones. Our results suggest that PCP signaling may regulate growth cone guidance, at least in part, by regulating local protein synthesis in the growth cones through via an interaction between Frizzled3 and FMRP.

In vitro studies have provided valuable insights to the function and mechanisms in axon guidance. In this chapter, we will introduce the rodent "open-book" assay, pre- or postcrossing explant culture and the dissociated neuron culture. They have been used to discover mechanism which we have gone on to validate or will confirm using in vivo genetic approaches.

Understanding biochemical and cellular mechanisms of how PCP components regulate axon guidance is important for understanding brain development and may lead to new therapeutic approaches for neural repair. Meanwhile, axonal growth cones are a highly polarized structure and are a great experimental system. Therefore, some of these novel mechanisms we are uncovering for axon guidance may be applicable for PCP signaling in general. In this chapter, we introduce some of the techniques we used or developed: (1) protein localization and trafficking; (2) protein phosphorylation; and (3) protein-protein interactions in the same cell and across the two neighboring cells.

Our lab showed that the Wnt family proteins can function as axon guidance molecules and the planar cell polarity (PCP) pathway mediates the function of Wnts in axon guidance. One of the key evidences was by identifying the axon guidance defects in knockout or conditional knockout animals. We utilized a variety of axon tracing and labeling techniques, including immunohistochemistry (IHC), DiI, BDA, and fluorescent reporters (GFP or tdTomato). These studies have primarily been conducted in spinal cord commissural axons, but have been applied to retinal ganglion cell axons, corticospinal tract axons, dopaminergic and serotonergic projections.

Description, The glutamatergic synapses are assembled and maintained by conserved planar cell polarity proteins., Whether there exists a common signaling mechanism that assembles all glutamatergic synapses is unknown. We show here that knocking out Prickle1 and Prickle2 reduced the formation of the PSD-95–positive glutamatergic synapses in the hippocampus and medial prefrontal cortex in postnatal development by 70–80%. Prickle1 and Prickle2 double knockout in adulthood lead to the disassembly of 70 to 80% of the postsynaptic-density(PSD)-95–positive glutamatergic synapses. PSD-95–positive glutamatergic synapses in the hippocampus of Prickle2E8Q/E8Q mice were reduced by 50% at postnatal day 14. Prickle2 promotes synapse formation by antagonizing Vangl2 and stabilizing the intercellular complex of the planar cell polarity (PCP) components, whereas Prickle2 E8Q fails to do so. Coculture experiments show that the asymmetric PCP complexes can determine the presynaptic and postsynaptic polarity. In summary, the PCP components regulate the assembly and maintenance of a large number of glutamatergic synapses and specify the direction of synaptic transmission.

Background: Whole-body plethysmography (WBP) is the gold standard for measuring lung volume, but its clinical application is limited as it requires expensive equipment and is not simple to use. Studies have shown that the single-breath helium dilution (SBHD) method, which is commonly used in clinical practice, significantly underestimates lung volume in patients with obstructive lung disease (OLD). By comparing the differences in lung volume measured using SBHD and WBP, we aimed to establish a correction equation for the SBHD method to determine the total lung volume in patients with OLD of different severities.Methods: From 628 patients with OLD simultaneously subjected to SBHD and WBP, 407 patients enrolled between January 2018 and November 2019 were in the training group and 221 enrolled between December 2019 and December 2020 were in the prospective verification cohort. The multiple linear regression equation was used for data in the training group to establish a correction equation for SBHD to determine the total lung volume, and this was validated in the prospective validation cohort.Results: There was a moderate positive correlation between total lung capacity (TLC) determined using the SBHD [TLC (SBHD)] and WBP methods [TLC (WBP)] (r = 0.701; P < 0.05), and the differences between TLC (SBHD) and TLC (WBP) (ΔTLC) were related to the severity of obstruction. As the severity of obstruction increased, the TLC was underestimated by the SBHD method. We established the following correction equation: TLC (adjusted SBHD) (L) = −0.669 + 0.756*TLC(SBHD)(L) – 0.047*FEV1FVC+0.039*height (cm)–0.009*weight(kg)(r2 = 0.753 and adjusted r2 = 0.751). Next, we validated this equation in the validation cohort. With the correction equation, no statistical difference was observed between TLC (adjusted SBHD) and TLC (WBP) among the obstruction degree groups (P > 0.05).Conclusions: The SBHD method is correlated with WBP to measure the total lung volume, but the SBHD method presents limitations in determining the total lung volume in patients with obstructive lung disease. Here, we established an effective and reliable correction equation in order to accurately assess the total lung volume of patients with OLD using the SBHD method.

Epithelial‑mesenchymal transition (EMT) provides a valuable source of fibroblasts that produce extracellular matrix in airway walls. The Sonic hedgehog (SHH) signaling pathway plays an essential role in regulating tissue turnover and homeostasis. SHH is strikingly upregulated in the bronchial epithelia during asthma. Snail1 is a major target of SHH signaling, which regulates EMT and fibroblast motility. The present study was designed to ascertain whether the combination of house dust mite (HDM) and transforming growth factor β1 (TGF‑β1) could induce EMT via the SHH signaling pathway in human bronchial epithelial cells (HBECs). HBEC cultures were treated with HDM/TGF‑β1 for different periods of time. The involvement of SHH signaling and EMT biomarkers was evaluated by quantitative real‑time PCR, western blotting and immunofluorescence staining. Small‑interfering RNA (siRNA) for glioma‑associated antigen‑1 (Gli1) or cyclopamine was used to inhibit SHH signaling in HBECs. HBECs stimulated by HDM/TGF‑β1 exhibited morphological features of EMT. E‑cadherin (an epithelial marker) was decreased after a 72‑h exposure to HDM/TGF‑β1 compared to that in the control cells, and the expression of type I collagen and FSP1 (mesenchymal markers) was increased. HDM/TGF‑β1 activated the SHH signaling pathway in HBECs, which led to Gli1 nuclear translocation and the transcriptional activation of Snail1 expression. Moreover, gene silencing or the pharmacological inhibition of Gli1 ameliorated EMT. In summary, these findings suggest that HDM/TGF‑β1 may induce EMT in HBECs via an SHH signaling mechanism. Inhibition of SHH signaling may be a novel therapeutic method for preventing airway remodeling in asthma.

Amino acid chirality has been recognized as an important driving force in constructing peptide architectures, via interactions such as chirality-induced stereochemical effect. The introduction of site-specific chiral conversion of l- and d-amino acids in peptide sequences could enable the pursuit of the chirality effects in peptide assembly. In this work, we characterized the assemblies of heptapeptides with various side chain moieties and their chiral variants using STM. Specifically, two pairs of amino acids, Gln (Q) and Asn (N), Glu (E) and Asp (D), having one methylene difference in their side chains, are selected to elucidate the steric dependence of amino acid chiral effects on surface-bound peptide assemblies. The observed heptapeptide assembly structures reveal that chirality switching of a single amino acid is able to destabilize the surface-mediated peptide assemblies, and this disturbance effect can be positively correlated with the steric hindrance of amino acid side chains. Furthermore, the strength of the impact due to chiral conversion on heptapeptide assembly structure is noticeably dependent on the mutation sites, indicative of structural heterogeneity of chiral effects. These results could contribute to the molecular insights of chirality-induced stereochemical interactions in peptide assembly.

Amyloid beta oligomers cause glutamatergic synapse degeneration by targeting the planar cell polarity components in the synapses., The signaling pathway directly controlling the maintenance of adult glutamatergic synapses has not been well understood. Planar cell polarity (PCP) signaling components were recently shown to play essential roles in the formation of glutamatergic synapses. Here, we show that they are localized in the adult synapses and are essential for their maintenance. Synapse loss at early stages of Alzheimer’s disease is thought to be induced by β-amyloid (Aβ) pathology. We found that oligomeric Aβ binds to Celsr3 and assists Vangl2 in disassembling synapses. Moreover, a Wnt receptor and regulator of PCP signaling, Ryk, is also required for Aβ-induced synapse loss. In the 5XFAD mouse model of Alzheimer’s disease, Ryk conditional knockout or a function-blocking monoclonal Ryk antibody protected synapses and preserved cognitive function. We propose that tipping of the fine balance of Wnt/PCP signaling components in glutamatergic synapses may cause synapse degeneration in neurodegenerative disorders with Aβ pathology.

Epilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1(PK1) gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PK1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a PK1R104Q mouse line. The mutant mice showed reduced density of excitatory synapses in hippocampus and impaired interaction between PK1 and the repressor element 1(RE-1) silencing transcription factor (REST). They also displayed reduced seizure threshold, impaired social interaction, and cognitive functions. Taken together, the PK1R104Q mice display characteristic behavioral features similar to the key symptoms of epilepsy and ASD, providing a useful model for studying the molecular and neural circuit mechanisms underlying the comorbidity of epilepsy and ASD.

We have examined in this contribution the composition dependence of binding characteristics in peptide-peptide interactions between an oligopeptide octa-glycine and a series of tryptophan-containing octapeptides. The binding energy associated with tryptophan-glycine interactions manifests pronounced stepwise binding characteristics as the number of tryptophan increases from 0 to 8 in the octapeptides consisting only of glycine and can be attributed to mono-, di-, and tri-valent peptide-peptide interactions. At the same time, only weak fluctuations in binding energy were observed as the number of tryptophan increases from 2 to 7. Such distinctive nonlinearity of composition-dependent tryptophan-glycine binding energy characteristics due to continuously varying tryptophan compositions in the octapeptides could be considered as a reflection of combinatorial contributions due to the hydrogen bonds originated from the indole moieties of tryptophan with the main chains of octapeptide of glycine containing N-H and C=O moieties and the van der Waals interactions (including π-π and π-CH interactions) between peptides.

Formation of viable but non-culturable (VBNC) status in methicillin-resistant Staphylococcus aureus (MRSA) has never been reported, and it poses a significant concern for food safety. Thus, this study aimed to firstly develop a rapid, cost-effective, and efficient testing method to detect and differentiate MRSA strains in the VBNC state and further apply this in real food samples. Two targets were selected for detection of MRSA and toxin, and rapid isothermal amplification detection assays were developed based on cross-priming amplification methodology. VBNC formation was performed for MRSA strain in both pure culture and in artificially contaminated samples, then propidium monoazide (PMA) treatment was further conducted. Development, optimization, and evaluation of PMA-crossing priming amplification (CPA) were further performed on detection of MRSA in the VBNC state. Finally, application of PMA-CPA was further applied for detection on MRSA in the VBNC state in contaminated food samples. As concluded in this study, formation of the VBNC state in MRSA strains has been verified, then two PMA-CPA assays have been developed and applied to detect MRSA in the VBNC state from pure culture and food samples.

Synapse loss is an early event in Alzheimer’s disease and is thought to be associated with amyloid pathology and caused by Amyloid β (Aβ) oligomers. Whether and how Aβ oligomers directly target signaling pathways for glutamatergic synapse maintenance is unknown. Glutamatergic synapse development is controlled by the opposing functions of Celsr3 and Vangl2, core components of the Wnt/planar cell polarity (PCP) signaling pathway, functioning directly in the synapses. Celsr3 promotes synapse formation, whereas Vangl2 inhibits synapse formation. Here we show that oligomeric Aβ binds to Celsr3 and assists Vangl2 in disassembling synapses by disrupting the intercellular Celsr3/Frizzled3-Celsr3 complex, essential for PCP signaling. Together with Vangl2, a Wnt receptor, Ryk, is also required for Aβ oligomer-induced synapse loss in a mouse model of Alzheimer’s disease, 5XFAD, where conditional Ryk knockout protected synapses and preserved cognitive function. Our study reveals a fine balance of Wnt/PCP signaling components in glutamatergic synapse maintenance and suggests that overproduced Aβ oligomers may lead to excessive synapse loss by tipping this balance. Together with previous reports that an inhibitor of Wnt/Ryk signaling, WIF1, is found reduced in Alzheimer’s disease patients, our results suggest that the imbalance of PCP signaling in these patients may contribute to synapse loss in Alzheimer’s disease and manipulating Wnt/PCP signaling may preserve synapses and cognitive function.

We demonstrate in this contribution the evidence that significant cooperative binding effect can be identified for the amino acid sites that are determinant to the binding characteristics in peptide-peptide interactions. The analysis of tryptophan-scanning mutagenesis of the 14-mer peptide consisting only of glycine provides a mapping of position-dependent contributions to the binding energy. The pronounced tryptophan-associated peptide-peptide interactions are originated from the indole moieties with the main chains of 14-mer glycines containing N-H and CO moieties. Specifically, with the presence of two tryptophans as determinant amino acids, cooperative binding can be observed, which are dependent on relative positions of the two tryptophans with a "volcano"-like characteristics. An optimal separation of 6-10 amino acids between two adjacent binding sites can be identified to achieve maximal binding interactions.

The characteristics of peptide conformations in both solution and surface-bound states, using poly-glycine as a model structure, are analyzed by using molecular dynamics (MD) simulations. The clustering analysis revealed significant linearization effect on the peptide conformations as a result of adsorption to surface, accompanied by varied adsorption kinetics and energetics. Depending on the inter-peptide interaction characteristics, distinctively different surface-mediated oligomerization modalities, such as antiparallel conformations, can be identified in MD and confirmed by scanning tunneling microscopy (STM) analysis of the assembly structures. These observations are beneficial for obtaining molecular insights of assembling propensity relating to peptide-surface and peptide-peptide interactions.

We have determined the interaction strengths of the common naturally occurring amino acids using a complete binding affinity matrix of 20 × 20 pairs of homo-octapeptides consisting of the 20 common amino acids between stationary and mobile states. We used a bead-based fluorescence assay for these measurements. The results provide a basis for analyzing specificity, polymorphisms, and selectivity of inter-amino-acid interactions. Comparative analyses of the binding energies, i.e., the free energies of association (ΔGA), reveal contributions assignable to both main-chain-related and side-chain-related interactions originating from the chemical structures of these 20 common amino acids. Side-chain–side-chain and side-chain–main-chain interactions are found to be pronounced in an identified set of amino acid pairs that determine the basis of inter-amino-acid recognition., Interaction strengths between common amino acids were measured with a bead-based fluorescence assay. The results provide a basis for analyzing specificity and selectivity of inter-amino-acid recognition.

The abnormal accumulation of beta-amyloids (Aβ) in brain is considered as a key initiating cause for Alzheimer's disease (AD) due to their richness in plaques and self-aggregate propensity. In recent studies, N-terminally extended Aβ peptides (NTE-Aβ) with the N-terminus originating prior to the canonical β-secretase cleavage site were found in humans and suggested to have possible relevance to AD. However, the effects of the extended N-terminus on the amyloidegenic structure and aggregation propensity have not been fully elucidated. Herein, we characterized the assembly structures of Aβ1-42, Aβ(-5)-42, Aβ(-10)-42 and Aβ(-15)-42 with both normal and reversed sequences on highly oriented pyrolytic graphite (HOPG) surfaces with scanning tunneling microscopy (STM). The molecularly resolved surface-mediated peptide assemblies enable identification of amyloidegenic fragments. The observations reveal that the assembly propensity of the C-terminal strand of Aβ1-42 is highly conserved and insensitive to N-terminal extensions. In contrast, different assembly structures of the N-terminal strand of Aβ variants can be observed with possible assignment of varied amyloidegenic fragments in the extended N-termini, which may contribute to the varied aggregation propensities of Aβ42 species.

Surface modification can impart nanostructures new interface properties. In this review, we summarize the representative surface modification methods of nanoparticles with peptides and proteins. The biomolecules can be conjugated with nanoparticles by noncovalent and covalent coupling. Both of these approaches have strengths and limitations. Physical adsorption is the most direct and simplest noncovalent method but peptides and proteins adsorbed on solid surface always loss their native structures and biological activity and the behavior of peptides and proteins on surface is still difficult to regulate precisely. A popular noncovalent conjugation with stability and selectivity is via biotin-streptavidin interaction. Covalent attachment is more stable and selective than noncovalent methods. The stability of covalent biomolecule-nanostructure conjugates makes this strategy useful for applications in biological media with other interfering species. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/ N -hydroxysuccinimide (NHS) strategy is widely used for covalent bioconjugation with well-established protocol, but it could lead to hydrolysis problem, crosslinking and uncontrolled heterogeneous orientation. The click chemistry is another covalent strategy with higher selectivity and yield, while it takes an extended reaction time. In addition to considering stability, selectivity, reaction time, and yield mentioned above, covalent bioconjugation should proceed in mild condition and the reagents required should have no interference on properties of biomolecules and nanostructures. In recent years substantial progress has been made in the formation of bionanoconjugates, but there is still no completely reliable approach for biomolecule-nanosturcture conjugation. Heretofore fine-tuning the structure and orientation of peptides and proteins on surface has been challenging. The efforts on improving biostability, biodistribution and targeting of nanoparticles with peptides and proteins functionalization are introduced. Nanostructures are often used within body in biomedical applications, so they must overcome an ensemble of biological obstacles to perform their function. First they may suffer from clearance from the bodys immune system. Even though they can escape from clearance, they are required to arrive their correct battlefield. Whats more, nanostructures need to cross cell membrane barriers and reach specific organelles such as nucleus and mitochondria to function in most cases. Peptide- and protein-nanostructure conjugation has been emerged as a useful tool to address these problems mentioned above. They could provide nanostrctures protection from phagocytic clearance and promote persistent circulation. Nanostructures can penetrate cell membrane easily with cell-penetrating peptide modification. The specific recognition of biological molecules imparts nanostructures targeting ability. In addition, the applications in fields such as diagnostics are introduced based on antigen-antibody specific recognition. The problems that bionanoconjugates for medical applications may encounter in use are presented briefly. Once contacting with biological matrices, nanostructures will be immediately coated by proteins, forming a protein corona. This protein layer could make significant changes in nanostructure properties such as size, surface charge and even the bioactivity of the peptides and proteins conjugated on its surface, which provides nanostructure with a new biological identity. Some previous results suggested that protein-functionalized nanoparticles lost their targeting capabilities when a protein corona adsorbed on the surface. In short, not only should bioconjugation methods be picked carefully depending on the goals, but also the effects of the complex use environment on bionanoconjugates should be taken into consideration. This review is intended to help researchers get an idea of the progress and dilemma of bionanoconjugate construction and its applications, and provide some inspiration for design and synthesis of peptide and protein-modified nanostructures.

In this review, we try to reflect the recent progress on assembly structures, aggregation behaviors and the cytotoxicity of beta amyloid (Aβ) peptides, which are closely related to the pathogenesis of Alzheimer’s disease (AD). Based on these studies, the progress on the regulation mechanism of various nanobiointerfaces in amyloid peptide assembly and aggregation structures is reviewed and discussed, especially the interaction patterns and mechanisms between Aβ peptides and nanomaterials on the molecule level. These progresses could help to deepen the insights of the complex interactions between amyloid peptides and modulators. To study Aβ peptide conformation, assembly mechanism and aggregation process, developing new efficient nanobiointerface modulators is of great importance for the therapeutic strategy evolution.

Implantable neural probes constitute an essential tool for neuronal activity recordings in basic neuroscience and also hold great promise for the development of neuroprosthesis to restore lost motor or sensory functions of the body. However, conventional neural probes are susceptible to biofouling because of their physicochemical mismatch with neural tissues, resulting in signal degradation in chronic studies. Here, we describe an ultraflexible neural probe (uFNP) with anti-fouling zwitterionic peptide modification for long-term stable neural activity recordings. The anti-fouling zwitterionic peptide consists of two parts: negatively charged glutamic acid (E) and positively charged lysine (K) formed EKEKEK (EK) head to create a hydration layer that resists protein adsorption on the microelectrodes, and a fragment of laminin formed IKVAV tail to increase the adhesion of the microelectrodes to neuronal cells. We demonstrate that EK-IKVAV modified uFNPs can allow for stable neuronal activity recordings over 16 weeks. Immunohistological studies confirm that EK-IKVAV functionalized uFNPs could induce greatly reduced neuronal cell loss. Collectively, these results suggest that the anti-fouling zwitterionic peptide functionalization of uFNPs provide a promising route to construct biocompatible and stable neural interfaces.