A continuum model of mechanosensation based on contractility kit assembly

Biophys J. 2024 Nov 8:S0006-3495(24)00708-2. doi: 10.1016/j.bpj.2024.10.020. Online ahead of print.

Abstract

The ability of cells to sense and respond to mechanical forces is crucial for navigating their environment and interacting with neighboring cells. Myosin II and cortexillin I form complexes known as contractility kits (CKs) in the cytosol, which facilitate a cytoskeletal response by accumulating locally at the site of inflicted stress. Here, we present a computational model for mechanoresponsiveness in Dictyostelium, analyzing the role of CKs within the mechanoresponsive mechanism grounded in experimentally measured parameters. Our model further elaborates on the established distributions and channeling of contractile proteins before and after mechanical force application. We rigorously validate our computational findings by comparing the responses of wild-type cells, null mutants, overexpression mutants, and cells deficient in CK formation to mechanical stresses. Parallel in vivo experiments measuring myosin II cortical distributions at equilibrium provide additional validation. Our results highlight the essential functions of CKs in cellular mechanosensitivity and suggest new insights into the regulatory dynamics of mechanoresponsiveness.