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Paper-based platforms for biological studies have received significant attention given that cellulose is ubiquitous, biocompatible, and can be readily organized into tunable fibrous structures. In the latter form, effect of complexity in surface morphologies (roughness, porosity and fiber organization) on cell-substrate interaction has not been thoroughly explored. We infer that altering the properties of a fibrous material should lead to significant changes in cellular microenvironment and direct the deposition of structurally analogous extracellular matrix (fiber-fiber templating) like collagen. Here, we elucidate the effect of varying paper roughness and surface chemistry on NIH/3T3 fibroblasts via organization of excreted collagen. Collagen intensity was found to increase linearly with paper porosity, indicating a 3D culture platform. The intensity, however, decays over time due to biodegradation of the substrate. Stability can be improved by introducing fluorinated alkyl silanes to yield hydrophobic paper. This process concomitantly transforms the substrate to a 2D-like scaffold where collagen is predominantly assembled on the surface, thus changing the cellular microenvironment. Altering surface energy also led to fluctuations in collagen intensity and organization over time for smooth (calendered) paper substrates. We infer that the increased roughness improves collagen adsorption through capillary driven petal effect. In general, the influence of the substrate simultaneously affects its ability to host collagen and guide orientation. These findings offer insights into the effects of secondary structures and chemistry of fibrous polymeric materials on cell culture, which we propose as vital parameters when using paper-based platforms. Unlabelled Image • Collagen secreted from NIH/3T3 fibroblast cells increases linearly with paper porosity. • Paper transitions from 3D to 2D cell culture scaffold when rendered hydrophobic. • Hydrophobic paper relies on capillary driven petal effect for collagen adsorption. [ABSTRACT FROM AUTHOR]

Introduction: The extracellular matrix (ECM) in the tumor microenvironment contains high densities of collagen that are highly aligned, resulting in directional migration called contact guidance that facilitates efficient migration out of the tumor. Cancer cells can remodel the ECM through traction force controlled by myosin contractility or proteolytic activity controlled by matrix metalloproteinase (MMP) activity, leading to either enhanced or diminished contact guidance.Methods: Recently, we have leveraged the ability of mica to epitaxially grow aligned collagen fibrils in order to assess contact guidance. In this article, we probe the mechanisms of remodeling of aligned collagen fibrils on mica by breast cancer cells.Results: We show that cells that contact guide with high fidelity (MDA-MB-231 cells) exert more force on the underlying collagen fibrils than do cells that contact guide with low fidelity (MTLn3 cells). These high traction cells (MDA-MB-231 cells) remodel collagen fibrils over hours, pulling so hard that the collagen fibrils detach from the surface, effectively delaminating the entire contact guidance cue. Myosin or MMP inhibition decreases this effect. Interestingly, blocking MMP appears to increase the alignment of cells on these substrates, potentially allowing the alignment through myosin contractility to be uninhibited. Finally, amplification or dampening of contact guidance with respect to a particular collagen fibril organization is seen under different conditions.Conclusions: Both myosin II contractility and MMP activity allow MDA-MB-231 cells to remodel and eventually destroy epitaxially grown aligned collagen fibrils. [ABSTRACT FROM AUTHOR]

Highlights • Liposomes were modified with arginine derivatives to target colon cancer cells. • Encapsulated doxorubicin in many modified liposomes exhibited improved toxicity. • Statistical correlations provide design rules for efficient cancer therapy. Abstract Liposomal encapsulation of chemotherapeutics improves circulation time and decreases off-target effects through the enhanced permeability and retention (EPR) effect. Improving the efficacy of these drug carriers through surface modification could benefit patients. A library of arginine derivatives was conjugated to liposomes through carbodiimide chemistry. Both unmodified and modified liposomes were loaded with doxorubicin and exposed to Caco-2 colon carcinoma cells to measure the half maximal inhibitory concentration (IC 50). Most of the modifications improved the toxicity of doxorubicin. Principal component analysis (PCA) was used to uncover correlations between physicochemical properties (lipophilicity (log P), partition coefficient (log D), number of hydrogen bond donors, number of hydrogen bond acceptors, freely rotating bonds, surface tension, polarization surface area, and isoelectric point) and the IC 50 of encapsulated doxorubicin. Generalized rules for improved toxicity were also developed, which stated that improved drug carriers should have at least 4 hydrogen bond donors, between 4 and 6 freely rotating bonds, an isoelectric point above 5.5, and a log P between -2 and -1. Using these relationships along with previously obtained correlations for macrophages, selective targeting and the understanding of how to rationally design such drug carriers can be improved. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the beneficial effect of low-power lasers and polarized light on wound healing, inflammation, and the treatment of rheumatologic and neurologic disorders. The overall effect of laser irradiation treatment is still controversial due to the lack of studies on the biochemical mechanisms and the optimal parameters for the incident light that should be chosen for particular applications. Here, we study how NIH/3T3 fibroblasts respond to irradiation with linearly polarized light at different polarization angles. In particular, we examined vascular endothelial growth factor (VEGF) secretion, differentiation to myofibroblasts, and collagen organization in response to 800 nm polarized light at 0°, 45°, 90°, and 135° with a power density of 40 mW/cm2 for 6 min every day for 6 days. Additional experiments were conducted in which the polarization angle of the incident was changed every day to induce an isotropic distribution of collagen. The data presented here shows that polarized light can upregulate VEGF production, myofibroblast differentiation, and induce different collagen organization in response to different polarization angles of the incident beam. These results are encouraging and demonstrate possible methods for controlling cell response through the polarization angle of the laser light, which has potential for the treatment of wounds. [ABSTRACT FROM AUTHOR]

Functionalized biomaterials interface with tissue upon implantation. There is a growing need to understand how materials properties influence this interaction so that efficient tissue engineering systems can be developed. In this study, we characterize collagen organization in response to functionalized glass beads implanted in SKH1-E mice. Poly- l -arginine (PLR) was modified with arginine derivatives to create a functionalized surface and was coated on glass beads. Tissue sections were removed 28 days post-implantation and were imaged using second harmonic generation (SHG) microscopy. These chemical modifications were able to alter the collagen distribution from highly aligned to disordered (17 ± 6 to 78 ± 1° full width at half-maximum (FWHM)) and the collagen III/I ratio (0.02 to 0.42). Principal component analysis (PCA) comparing the physical properties of the modifiers (e. g. hydrophobicity, molar volume, freely rotating bonds, polarizability) with the SHG analytically derived parameters (e. g. collagen III/I ratio, collagen orientation) was performed. Chemical properties of the PLR-like modifications including lipophilicity, along with the number of freely rotating bonds and the polarizability had significant effects on the collagen surrounding the implant, both in terms of collagen orientation as well as the production of collagen III. These findings demonstrate the possibility of tuning the foreign body response, in terms of collagen deposition and organization, to positively influence the acceptance of implanted biomaterials. • Poly- l -arginine modifications were coated on glass beads to study fibrotic response • Second harmonic generation imaging visualized collagen deposition and organization • Creatinine and albizziin modifications derived contrasting collagen III responses • Principal component analysis compared factors influencing implant acceptance [ABSTRACT FROM AUTHOR]