Direct measurement of the lamellipodial protrusive force in a migrating cell

TLDR

Lamellipodial protrusion has attracted extensive study, yet the force generated by this process has never been directly measured. The authors used an atomic force microscopy cantilever positioned in the path of a migrating keratocyte, whose ∼10‑second deflection directly measures the lamellipodial leading‑edge force. Measured stall forces suggest ~100 polymerizing actin filaments per micrometer generate several piconewtons each, but the force‑velocity curves—showing a sharp velocity drop under tiny loads, insensitivity to low loads, and rapid stalling at high loads—contradict current actin‑polymerization models and imply a complex multiphase process involving actin and adhesion dynamics. Published in Cell, 2003, vol.

Abstract

There has been a great deal of interest in the mechanism of lamellipodial protrusion (Pollard, T., and G. Borisy. 2003. Cell. 112:453–465). However, one of this mechanism's endpoints, the force of protrusion, has never been directly measured. We place an atomic force microscopy cantilever in the path of a migrating keratocyte. The deflection of the cantilever, which occurs over a period of ∼10 s, provides a direct measure of the force exerted by the lamellipodial leading edge. Stall forces are consistent with ∼100 polymerizing actin filaments per micrometer of the leading edge, each working as an elastic Brownian ratchet and generating a force of several piconewtons. However, the force-velocity curves obtained from this measurement, in which velocity drops sharply under very small loads, is not sensitive to low loading forces, and finally stalls rapidly at large loads, are not consistent with current theoretical models for the actin polymerization force. Rather, the curves indicate that the protrusive force generation is a complex multiphase process involving actin and adhesion dynamics.