Collective pack size during cell migration modulated by an apparent cell-substrate friction

Collective cell migration is a dynamic biophysical phenomenon that is critical for wound healing, tumor invasion, and development. Cells are active and as such they produce cell-substrate and cell-cell forces which balance to bring about motion. During collective migration, cells form cohesive groups such as finger-like protrusions and coordinated packs; however, the underlying physical mechanisms controlling the size of these packs remain unclear. In most theoretical models, the connection between force and motion is governed by an apparent viscous friction at the cell-substrate interface. Here we conduct experiments to test two physics-based theoretical models that relate cell-substrate friction to either the size of a collective pack within the monolayer or the size of a protrusion at the leading edge. Increasing both time in culture and substrate stiffness affected the pack size within the monolayer and the protrusion size at the leading edge in a manner consistent with increased cell-substrate friction in the theoretical models. Thus, our experimental observations suggest that the size of collective cell packs and of protrusions at the edge of a cell layer depend on the magnitude of cell-substrate friction.