Computational Model for Cell Shape Regulation through Mechanosensing and Mechanical Feedback

Abstract

In response to both intracellular and extracellular signals, cells undergo controlled changes in morphology, which form a fundamental step in many developmental processes, including tissue morphogenesis and organogenesis. These changes require a means for sensing and interpreting the signaling cues, for generating the forces that act on the cell's physical material, and a control system that regulates this process. Identifying the molecular mechanisms that drive and regulate cell shape changes is a great challenge in the field of cell biology.In studies of dividing Dictyostelium discoideum amoebae, it has been shown that force-generating proteins could be localized in response to external mechanical perturbations. This mechanosensing, and the ensuing mechanical feedback, is believed to play an important role in minimizing the effect of mechanical disturbances during cell division. Owing to the complexity of the feedback system, which couples mechanical and biochemical signals involved in shape regulation, it is essential to develop theoretical approaches that can guide further experimentation and investigation.Here, we present a mechano-chemical computational model that explains the different mechanosensory and mechanoresponsive behaviors observed in Dictyostelium cells.This model expands a multi-scale myosin bipolar thick filament assembly model that incorporates cooperative and force-dependent myosin-actin binding, by identifying the feedback mechanisms hidden in the observed mechanoresponsive behaviors (monotonic vs. oscillatory) of Dictyostelium cells in the micropipette aspiration experiments. By doing so, we can explain the mechanism behind different modes of cellular retraction and hence cell shape regulation.