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Cell spreading and motility on an adhesive substrate are driven by the activephysical forces generated by the actin cytoskeleton. We have recently shownthat coupling curved membrane complexes to protrusive forces, exerted by theactin polymerization that they recruit, provides a mechanism that can give riseto spontaneous membrane shapes and patterns. In the presence of an adhesivesubstrate, this model was shown to give rise to an emergent motile phenotype,resembling a motile cell. Here, we utilize this ``minimal-cell" model toexplore the impact of external shear flow on the cell shape and migration on auniform adhesive flat substrate. We find that in the presence of shear themotile cell reorients such that its leading edge, where the curved activeproteins aggregate, faces the shear flow. The flow-facing configuration isfound to minimize the adhesion energy by allowing the cell to spread moreefficiently over the substrate. For the non-motile vesicle shapes, we find thatthey mostly slide and roll with the shear flow. We compare these theoreticalresults with experimental observations, and suggest that the tendency of manycell types to move against the flow may arise from the very general, andnon-cell-type-specific mechanism predicted by our model.

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