Stochastic fluctuation-induced cell polarization on elastic substrates: A cytoskeleton-based mechanical model

Mechanical cues from the microenvironments play an important role in many physiological and pathological processes, e.g., stem cell differentiation and cancer cell metastasis. Recent experiments showed that the spreading and polarization of cells are highly associated with the substrate rigidity. However, the underlying mechanisms of these cell behaviors are still unknown. Here, we develop a cytoskeleton-based mechanical model to study the cell morphology on substrates of various rigidities, and carry out the experiments of mouse embryo fibroblasts on hydrogels of different rigidities. Our theoretical model involves both biomechanical and biochemical mechanisms, including actin polymerization, myosin motors contractility, integrin binding dynamics, membrane deformation and substrate stiffness. Using this model, we can simulate the spatiotemporal evolution of cell morphology on substrates of various rigidities. Interestingly, we find that the stochastic fluctuation in the initial cell shape can lead to the spontaneous generation of cell polarization on elastic substrates. Moreover, a cell can exhibit a more anisotropic geometry on stiff substrates than on soft ones. Our theoretical predictions are in good agreement with experimental results. The proposed model is capable of exploring the cell morphology regulated by substrate rigidities, and sheds lights on the functioning of cellular mechanosensing systems.