A minimal mechanosensing model predicts keratocyte evolution on flexible substrates.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang Z
PROVIDER: S-EPMC7276546 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Substrate topographic patterning is a powerful tool that can be used to manipulate cell shape and orientation. To gain a better understanding of the relationship between surface topography and keratocyte behavior, surface patterns consisting of linear aligned or orthogonally aligned microchannels were used. Photolithography and polymer molding techniques were used to fabricate micropatterns on the surface of polydimethylsiloxane (PDMS). Cells on linear aligned substrates were elongated and aligned in the channel direction, while cells on orthogonal substrates had a more spread morphology. Both linear and orthogonal topographies induced chromatin condensation and resulted in higher expressions of keratocyte specific genes and sulfated glycosaminoglycans (sGAG), compared with non-patterned substrates. However, despite differences in cell morphology and focal adhesions, many genes associated with a native keratocyte phenotype, such as keratocan and ALDH3A1, remain unchanged on the different patterned substrates. This information could be used to optimize substrates for keratocyte culture and to develop scaffolds for corneal regeneration.
| S-EPMC7174307 | biostudies-literature
Project description:Polymerized polyacrylamide
| S-EPMC9301700 | biostudies-literature
Project description:AbstractIn this work, we used nanosphere lithography to fabricate large area 2-D magnetic nanoparticle (MNP) arrays on a flexible polyimide substrate (Kapton). Samples were fabricated by assembling polystyrene (PS) spheres on thin films of Co capped with Au. Etched PS spheres were used to mask Co-Au particle arrays. The MNP arrays were subjected to superconducting quantum interference device measurements; flat samples (10 nm Co coated with 10 nm Au) exhibited an M s of 117.3 emu g-1, which was lower than the reported literature value for bulk Co (162.7 emu g-1). When compared to the flat film, coercivity, H c, increased in a linear fashion with respect to particle size. These preliminary results reveal that future investigations of the magnetic properties on flexible substrates should account for residual Co remaining in the polymeric material, the unique MNP shape, the effect of order (or lack or order) of the 2D array, and positioning with respect to the direction of the magnetic field.Graphical abstractSupplementary informationThe online version contains supplementary material available at 10.1557/s43580-021-00193-z.
| S-EPMC8783782 | biostudies-literature
Project description:BACKGROUND: The importance of peptide microarrays as a tool for serological diagnostics has strongly increased over the last decade. However, interpretation of the binding signals is still hampered by our limited understanding of the technology. This is in particular true for arrays probed with antibody mixtures of unknown complexity, such as sera. To gain insight into how signals depend on peptide amino acid sequences, we probed random-sequence peptide microarrays with sera of healthy and infected mice. We analyzed the resulting antibody binding profiles with regression methods and formulated a minimal model to explain our findings. RESULTS: Multivariate regression analysis relating peptide sequence to measured signals led to the definition of amino acid-associated weights. Although these weights do not contain information on amino acid position, they predict up to 40-50% of the binding profiles' variation. Mathematical modeling shows that this position-independent ansatz is only adequate for highly diverse random antibody mixtures which are not dominated by a few antibodies. Experimental results suggest that sera from healthy individuals correspond to that case, in contrast to sera of infected ones. CONCLUSIONS: Our results indicate that position-independent amino acid-associated weights predict linear epitope binding of antibody mixtures only if the mixture is random, highly diverse, and contains no dominant antibodies. The discovered ensemble property is an important step towards an understanding of peptide-array serum-antibody binding profiles. It has implications for both serological diagnostics and B cell epitope mapping.
| S-EPMC3311590 | biostudies-literature
Project description:Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls dendritic filopodia dynamics.
| S-EPMC5391179 | biostudies-literature
Project description:In cell proliferation, stem cell differentiation, chemoresistance, and tissue organization, the ubiquitous role of YAP/TAZ continues to impact our fundamental understanding in numerous physiological and disease systems. YAP/TAZ is an important signaling nexus integrating diverse mechanical and biochemical signals, such as ECM stiffness, adhesion ligand density, or cell-cell contacts, and thus strongly influences cell fate. Recent studies show that YAP/TAZ mechanical sensing is dependent on RhoA-regulated stress fibers. However, current understanding of YAP/TAZ remains limited due to the unknown interaction between the canonical Hippo pathway and cell tension. Furthermore, the multiscale relationship connecting adhesion signaling to YAP/TAZ activity through cytoskeleton dynamics remains poorly understood. To identify the roles of key signaling molecules in mechanical signal sensing and transduction, we present a, to our knowledge, novel computational model of the YAP/TAZ signaling pathway. This model converts extracellular-matrix mechanical properties to biochemical signals via adhesion, and integrates intracellular signaling cascades associated with cytoskeleton dynamics. We perform perturbations of molecular levels and sensitivity analyses to predict how various signaling molecules affect YAP/TAZ activity. Adhesion molecules, such as FAK, are predicted to rescue YAP/TAZ activity in soft environments via the RhoA pathway. We also found that changes of molecule concentrations result in different patterns of YAP/TAZ stiffness response. We also investigate the sensitivity of YAP/TAZ activity to ECM stiffness, and compare with that of SRF/MAL, which is another important regulator of differentiation. In addition, the model shows that the unresolved synergistic effect of YAP/TAZ activity between the mechanosensing and the Hippo pathways can be explained by the interaction of LIM-kinase and LATS. Overall, our model provides a, to our knowledge, novel platform for studying YAP/TAZ activity in the context of integrating different signaling pathways. This platform can be used to gain, to our knowledge, new fundamental insights into roles of key molecular and mechanical regulators on development, tissue engineering, or tumor progression.
| S-EPMC4922562 | biostudies-literature
Project description:The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated the search for physical links between the observed genetic and dynamic cooperativity. We outline here a simplified theory of protein, which relates sequence correlations to physical interactions and to the emergence of mechanical function. Our protein is modeled as a strongly coupled amino acid network with interactions and motions that are captured by the mechanical propagator, the Green function. The propagator describes how the gene determines the connectivity of the amino acids and thereby, the transmission of forces. Mutations introduce localized perturbations to the propagator that scatter the force field. The emergence of function is manifested by a topological transition when a band of such perturbations divides the protein into subdomains. We find that epistasis-the interaction among mutations in the gene-is related to the nonlinearity of the Green function, which can be interpreted as a sum over multiple scattering paths. We apply this mechanical framework to simulations of protein evolution and observe long-range epistasis, which facilitates collective functional modes.
| S-EPMC5960285 | biostudies-literature
Project description:The integration of nanocomposite thin films with combined multifunctionalities on flexible substrates is desired for flexible device design and applications. For example, combined plasmonic and magnetic properties could lead to unique optical switchable magnetic devices and sensors. In this work, a multiphase TiN-Au-Ni nanocomposite system with core-shell-like Au-Ni nanopillars embedded in a TiN matrix has been demonstrated on flexible mica substrates. The three-phase nanocomposite film has been compared with its single metal nanocomposite counterparts, i.e., TiN-Au and TiN-Ni. Magnetic measurement results suggest that both TiN-Au-Ni/mica and TiN-Ni/mica present room-temperature ferromagnetic property. Tunable plasmonic property has been achieved by varying the metallic component of the nanocomposite films. The cyclic bending test was performed to verify the property reliability of the flexible nanocomposite thin films upon bending. This work opens a new path for integrating complex nitride-based nanocomposite designs on mica towards multifunctional flexible nanodevice applications.
| S-EPMC11314696 | biostudies-literature
Project description:Engineered tissues require enhanced organization of cells and extracellular matrix (ECM) for proper function. To promote cell organization, substrates with controlled micro- and nanopatterns have been developed as supports for cell growth, and to induce cellular elongation and orientation via contact guidance. Micropatterned ultra-thin biodegradable substrates are desirable for implantation in the host tissue. These substrates, however, need to be mechanically robust to provide substantial support for the generation of new tissues, to be easily retrievable, and to maintain proper handling characteristics. Here, we introduce ultra-thin (<10 ?m), self-assembled chitin nanofiber substrates micropatterned with replica molding for engineering cell sheets. These substrates are biodegradable, mechanically strong, yet flexible, and easily manipulated into the desired shape. As a proof-of-concept, fibroblast cell proliferation, elongation, and alignment were studied on the developed substrates with different pattern dimensions. On the optimized substrates, the majority of the cells aligned (<10°) along the major axis of micropatterned features. With the ease of fabrication and mechanical robustness, the substrates presented herein can be utilized as versatile system for the engineering and delivery of ordered tissue in applications such as myocardial repair.
| S-EPMC3809896 | biostudies-literature
Project description:Self-cleaning and/or photocatalytic films on polymer substrates have found numerous applications during the past decades. However, the common demand for high-temperature post synthesis treatment limits the application to temperature resistant substrates only. Herein, we prepared self-cleaning photocatalytic films on four thermosensitive polymeric substrates: polyvinyl chloride (PVC), polymethyl methacrylate (PMMA), and acryl coated polyester (PES) fabric (D2) with poly(vinylidene fluoride) (PVDF) containing lacquer (D1). TiO₂ was prepared via a low-temperature sol-gel process using titanium(IV) isopropoxide and zirconium(IV) butoxide as precursors with various loading levels of Zr; 0, 5, 10, and 20 mol.%, and deposited on the substrates by using a SiO₂ binder in form of thin films (ca. 200 nm thick) via dip-coating. The films were characterized by SEM, hardness test, UV-Vis, photothermal beam deflection spectroscopy, and IR spectroscopy, while photocatalytic activity was measured by the fluorescence-based method of the terephthalic acid probe and wetting by contact angle measurements. Films containing 10 mol.% of Zr showed the best compromise regarding photocatalytic activity and mechanical stability while from substrates point of view PVC performed the best, followed by PMMA, D1, and D2. The beneficial role of SiO₂ binder was not only guaranteeing excellent mechanical stability, but also to prevent the D1 polymer from deterioration; the latter was found to be labile to long-term solar-light exposure due to degradation of the top PVDF layer.
| S-EPMC6213899 | biostudies-literature