真核细胞运动接触抑制行为的力学-化学耦合模拟

Abstract

Contact inhibition of locomotion (CIL) drives various biological phenomena, including cell dispersion, collective cell migration, and cancer invasion. Based on our previously proposed cell migration model with multilayered signaling cascades, a mechanical-chemical coupling model for CIL was developed by further incorporating cell-cell contact-dependent signaling pathways to guide the cytoskeleton remodeling. The cell structure model incorporates a discrete actin filament network within a cycle. The entire mathematical model is composed of nonlinear diffusion-reaction equations coupled with force-balance equations and solved numerically by the in-house built LBP-D1Q3 method. Numerical simulations indicated that the manifestation of distinct CIL behavior depends on the cooperation between FilGAP-FLNa and N-cadherin signaling pathways in terms of Rho GTPase signaling. After achieving a suitable inhibitory effect of FilGAP, the cells retain moderate polarity, which can be reversed in response to N-cadherin signaling, leading to normal CIL behavior. The lack of FilGAP transforms the cells to a fully polarized state, which is difficult to reverse, thus leading to the “bypass” behavior. The lack of N-cadherin signaling prevents cells from repolarizing in response to cell-cell contact, leading to static cell-cell adhesion. These simulations provide a theoretical basis for understanding the effect of contact inhibition signaling on cell migration.