MECHANOCHEMICAL COUPLING MODEL AND NUMERICAL SIMULATION FOR CELL-CELL ADHESION IN SUSPENDED EPITHELIAL CELLS

Epithelial cells develop adherens junctions via local recruitment of a transmembrane receptor, named E-cadherin, whose activity is dependent on Ca^2+ signal. Growing evidences indicate the importance of tensile forces within actomyosin cortex, yet a system-level understanding for the mechanosensitive responses of cell-cell contacts remains unclear. Here, we constructed a mechanochemical coupling model, in which the tensile forces presented at adherens junctions participated in the interactions between myosin contractility, actin dynamics and local E-cadherin recruitment, which together, formed a mechanical feedback loop (MFL). The mechanical interactions between a pair of epithelial cells were treated by a motor-clutch mechanism. The in-house developed lattice-Boltzmann particle (LBP)-D1Q3 method, which had been embedded with a simple Monte-Carlo method, was adopted to solve the coupled nonlinear reaction-diffusion equations, which had stochastic reaction terms, and were coupled with the equilibrium differential equation. The numerical simulation results indicate that the spatiotemporal effects of MFL may arise an initial anisotropy in the distribution pattern of E-cadherin, which could be further amplified by "cis" interactions between E-cadherins from the same cell surface. The model thus confirms three distinct phases in the profile of E-cadherin accumulation at the center of contact zone, which are initial, rapid increase, and slowly increase, as observed experimentally. Furthermore, local recruitment of E-cadherin can be mechanically regulated by either the elastic modulus of actomyosin cortex or the extent of cell-cell contact, whereupon the highest E-cadherin density takes place at 1.2 rad. Accordingly, decreasing the elastic modulus of actomyosin cortex may thus act as a triggering mechanism for MFL while the length of cell-cell contact is denoted as a controller of the maturity of adherens junctions.