Cell adhesion is a coordinated dynamic process that regulates cellular functions, such as cell proliferation, migration, differentiation, embryonic morphogenesis, and disease progression. In this paper, a discrete mechanical model for cell adhesion to a substrate is established to study the effect of substrate stiffness on cell spreading. The stiffness of the adhesion substrates can be tuned by adjusting the maximum adhesive forces balanced by substrates. The model provides reliable and reasonable predictions of cellular morphology during cell spreading on various substrates, as well as the subcellular stress distribution at focal adhesion sites. The model opens the possibility of investigating cell mechanical behaviors and cell functions at the subcellular level and further facilitates experimental studies where cell mechanics plays an important role in disease states.

PDMS (Polydimethylsiloxane) chips are increasingly important for the application of fluorescence measurements due to their auto-fluorescence free, excellent transparency, and biocompatibility. However, the design of PDMS microfluidic chips requires to fabricate plenty of molds for structure optimization, resulting in high cost. In the present, PDMS chips with nafion membrane were fabricated by simple and low-cost method for bull serum albumin (BSA) enrichment. To optimize the laser cutting and bonding parameters, simulation models were established using Bilinear Kinematic and Mooney-Rivlin models, respectively. The influence of laser power and cutting speed on the width and depth of the micro-channels was investigated. And the effect of bonding pressure on the deformation of PDMS micro-channel and stress distribution near the micro-channels was also analyzed. The leakage test and BSA enrichment demonstrated the practicability and feasibility of the present fabrication method in this work.

Mechanosensing of cells to extracellular matrix (ECM) is highly active and plays a crucial role in various physiological processes. Growing numbers of studies provide evidence that cell sensitivity to ECM stiffness is a complex stress-strain feedback process. However, the mechanisms that rule this process are still not fully known. Here, an alternative mechanosensing scheme of cells, which is different from the previous myosin-II-based mechanisms, is proposed by employing the tension in cortical cytoskeletons (CSKs) as a force module to probe the substrate. The molecular mechanotransduction from cortical CSKs, through actin filaments and focal adhesions, and finally to the substrate, is mechanically modeled to scale the dynamic traction forces of cells. The developed model captures the characteristic spread of cells with respect to ECM stiffness whereby the spread is fully developed on a stiff substrate but not on a soft one. Furthermore, durotactic migration of cells on an elastic-gradient substrate is successfully modeled by the current method. The cells are concluded to migrate, actuated by the polarized traction forces from the stiffness gradient of the substrate and the stiffness matching between cells and substrate. Finally, the cells are proposed to actively target the preferred substrate by following a rule of mechanical matching between cells and substrate. This study provides a theoretical tool to advance our knowledge regarding the passive mechanical properties and the active sensing of cells, and further promotes the discovery of mechanosensing mechanisms as well as the material design for embryonic development and tissue homeostasis.

Cell polarization is crucial in most physiological functions. Living cells at the extracellular matrix (ECM) actively coordinate a polarized morphology to target the preferred signals. In particular, the initial heterogeneity of subcellular components, termed as structural polarity, has been discovered to mediate the early attachment and transmigration of cells in tumour metastasis. However, how heterogeneous cells initiate the early polarization remains incompletely discovered. Here, we establish a multiscale model of a cell to explore the chemo-mechanical mechanisms of cell polarization initiated by structural polarity. The two-dimensional vertex model of the cell is built with the main mechanical components of eukaryotic cells. The initial structural polarity of the modeled cell is introduced by seeding heterogeneous actin filaments at the cell cortex and quantified by the ratio of the filamentous forces at the vertices. Then, the structural polarity is integrated in the reaction–diffusion system of Rho GTPase (Cdc42) at the cell cortex to obtain the traction forces at the leading vertices. Finally, the modeled cell is actuated to spread under the traction forces and discovered to develop into a characteristic polarized morphology. The results indicate that the cell polarization is initiated and dynamically developed by structural polarity through the reaction–diffusion system of Cdc42. In addition, the bistability of Cdc42 activation at the cell cortex is defined and discovered to dominate the polarization status of the cell. Furthermore, biphasic (i.e., positive and negative) durotaxis of the cell is successfully modeled at an ECM with a stiffness gradient, and concluded to be codetermined by the chemo-mechanical coupling of the initial structural polarity and ECM stiffness gradient. The proposed multiscale model provides a quantitative way to probe cell polarization coupled with mechanical stimuli, biochemical reaction and cytoskeletal reorganization, and holds the potential to guide studies of cell polarization under multiple stimuli.