Two Distinct Actin Networks Drive the Protrusion of Migrating Cells

TLDR

Cell migration initiates by extension of the actin cytoskeleton at the leading edge. Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed that this process is mediated by two spatially colocalized but kinematically, molecularly, and functionally distinct actin networks. A lamellipodium network assembles at the leading edge but disassembles within 1–3 µm and only weakly couples to the cytoskeleton, driving random protrusion and retraction, whereas productive cell advance depends on a second colocalized lamella network that integrates actomyosin contraction with substrate adhesion.

Abstract

Cell migration initiates by extension of the actin cytoskeleton at the leading edge. Computational analysis of fluorescent speckle microscopy movies of migrating epithelial cells revealed this process is mediated by two spatially colocalized but kinematically, kinetically, molecularly, and functionally distinct actin networks. A lamellipodium network assembled at the leading edge but completely disassembled within 1 to 3 micrometers. It was weakly coupled to the rest of the cytoskeleton and promoted the random protrusion and retraction of the leading edge. Productive cell advance was a function of the second colocalized network, the lamella, where actomyosin contraction was integrated with substrate adhesion.