Mechanical-chemical coupling simulation of contact inhibition of locomotion in eukaryotic cells
SCIENTIA SINICA-PHYSICA MECHANICA & ASTRONOMICA(2022)
摘要
Contact inhibition of locomotion (CIL) drives various biological phenomena, including cell dispersion, collective cell mi-gration, 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 signal-ing 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 mod-erate 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.
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关键词
cytoskeleton remolding, mechanosensitive signaling pathway, Boltzmann method
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