Theory of cell size regulation underlying the onset of migration in adhered cells

Cell migration is closely linked to cell shape, yet cell size is often assumed to remain constant. This assumption is challenged by recent experiments showing that cells undergo volume loss during spreading and swelling upon activation, with migration velocity correlated to cell size. In this work, we present a minimal theoretical framework for cellular size regulation and its influence on migration velocity. We connect cell size to membrane potential and active, actin-driven forces. Spatial inhomogeneities in these forces establish cell polarization and drive migration. Crucially, inhomogeneity is easier to establish over larger sizes, giving rise to a critical contact area, above which migration is possible. Our theory captures the coupled dynamics of cell volume, surface area, and motility and explains recent experiments on neutrophils.