Cell migration by graded attachment to substrates and contraction

The migration of fibroblastic cells in vitro involves the extension of lamellipodia, attachment of the cytoskeleton through the plasma membrane to the extracellular matrix, and the generation of force that pulls attachments rearward and the cell forward. Bulk flow of membrane or lipid relative to the cell outline cannot be detected; however, crosslinked glycoproteins attached to the cytoskeleton move rearward and diffusing particles are driven forward by a motor mechanism. The leading edge is the preferential site for the cytoskeleton to attach to crosslinked glycoproteins including integrins. Force for moving the cell forward can be generated either by a cortical contraction acting as a net to pull the endoplasm forward or by motors at the boundary of the endoplasm and ectoplasm pulling on the cortical actin. As the cortical actin is anchored to the external matrix more strongly at the front of the cell than at the rear, contraction will pull the cell forward. Such a model has important implications for the nature of the glycoprotein attachments to the cytoskeleton and the regional differences in membrane structure.