A computational investigation on the membrane dynamics during different cellular processes

Abstract

Cell membrane is a phospholipid bilayer with various proteins embedded within. Physically, the mobile phospholipids give both fluidity and elasticity to the membrane as well as restrict the lateral diffusion transmembrane proteins. Although many theoretical models have been proposed to describe the behavior of the cell membrane, its combined fluidand solid-like nature has never been considered in a unified manner. Here we present a novel computational framework to address this outstanding issue where the in-plane diffusion of lipid molecules as well as the bending and shearing of the bilayer associated with the its out-of-plane movement have all been taken into account. In addition, the tension and bending moment-regulated transport of proteins within the membrane is also considered in our model, allowing it to be used to investigate cellular processes such as cell adhesion and cell division where membrane deformation and the functioning of non-uniformly distributed transmembrane proteins are known to play key roles. Finally, a Langevin dynamics based approach, i.e. by introducing a random force distribution over the membrane, is implemented in the model to capture thermal fluctuations of the cell membrane, whose validity was verified by comparing simulation results with a variety of theoretical predictions. We then use the computational model to study the dynamics of cell substrate or cell-cell adhesion during its early formation stage. Here, the deformability of the substrate is represented by an array of linear springs while the binding and unbinding kinetics between receptor and ligand molecules, responsive for bringing two surfaces together, is simulated via Monte Carlo method. Effectively, the coupling among the deformations of membrane, substrate and ligand- receptor bond, as well as the diffusion of adhesion molecules within the membrane and its their force-regulated binding kinetics, has been explicitly taken into account, making our investigation different most existing ones where usually only specific aspects of the adhesion process were considered. Interestingly, our simulations indicated that higher adhesion strength was achieved on stiffer substrates which is consistent with recent experiments. In addition, by examining the distributions of closed bonds and free receptors (within the membrane) during the adhesion process, it was also found that more close contact regions between the cell and substrate (where closed bonds aggregate) were formed on stiffer substrate, leading to larger macroscopic adhesion area. Finally, it was observed that, not surprising, stronger adhesion strength will be induced by higher receptor density, again in agreement with experimental observations. (417 words)