Modelling how curved active proteins and shear flow pattern cellular shape and motility

Front Cell Dev Biol. 2023 May 31:11:1193793. doi: 10.3389/fcell.2023.1193793. eCollection 2023.

Abstract

Cell spreading and motility on an adhesive substrate are driven by the active physical forces generated by the actin cytoskeleton. We have recently shown that coupling curved membrane complexes to protrusive forces, exerted by the actin polymerization that they recruit, provides a mechanism that can give rise to spontaneous membrane shapes and patterns. In the presence of an adhesive substrate, this model was shown to give rise to an emergent motile phenotype, resembling a motile cell. Here, we utilize this "minimal-cell" model to explore the impact of external shear flow on the cell shape and migration on a uniform adhesive flat substrate. We find that in the presence of shear the motile cell reorients such that its leading edge, where the curved active proteins aggregate, faces the shear flow. The flow-facing configuration is found to minimize the adhesion energy by allowing the cell to spread more efficiently over the substrate. For the non-motile vesicle shapes, we find that they mostly slide and roll with the shear flow. We compare these theoretical results with experimental observations, and suggest that the tendency of many cell types to move against the flow may arise from the very general, and non-cell-type-specific mechanism predicted by our model.

Keywords: adhesion; cell motility; curved membrane protein; cytoskeleton; shear flow.

Grants and funding

NSG is the incumbent of the Lee and William Abramowitz Professorial Chair of Biophysics, and acknowledges support by the Ben May Center for Theory and Computation, and the Israel Science Foundation (Grant No. 207/22). This research is made possible in part by the historic generosity of the Harold Perlman Family. AI and SP were supported by the Slovenian Research Agency (ARRS) through the Grant No. J3-3066 and J2-4447 and Programme No. P2-0232.