Cells migrate through a crowded environment during processes such as metastasis or wound healing, and must generate and withstand substantial forces. The cellular motility responses to environmental forces are represented by their force-velocity relation, which has been measured for fish keratocytes but remains unexplained. Even pN opposing forces slow down lamellipodium motion by three orders of magnitude. At larger opposing forces, the retrograde flow of the actin network accelerates until it compensates for polymerization, and cell motion stalls. Subsequently, the lamellipodium adapts to the stalled state. We present a mechanism quantitatively explaining the cell's force-velocity relation and its changes upon application of drugs that hinder actin polymerization or actomyosin-based contractility. Elastic properties of filaments, close to the lamellipodium leading edge, and retrograde flow shape the force-velocity relation. To our knowledge, our results shed new light on how these migratory responses are regulated, and on the mechanics and structure of the lamellipodium.

Cell motility is a fundamental process associated with many phenomena in nature, such as immune response, wound healing, and cancer metastasis. In these processes, cells must squeeze through cell layers, and we characterize this ability to actively produce forces and simultaneously adapt their shapes. We have measured forward forces up to 15 nN that a migrating keratocyte was able to generate, in order to adjust its shape and successfully force its way under and past an obstacle. We also observed that 34 nN was capable of stalling the cell's forward motion. Furthermore, we measured that under compression stresses up to 1,165 pN/micro m2 (1,165 Pa), cell morphology, and velocity remained unchanged. Additionally, we found that keratocytes were able to compress themselves up to 80% vertically in order to squeeze through a gap as small as 500 nm.

No abstract

No abstract

Confronting motile cells with obstacles doubling as force sensors we tested the limits of the driving actin and myosin machinery. We could directly measure the force necessary to stop actin polymerization as well as the force present in the retrograde actin flow. Combined with detailed measurements of the retrograde flow velocity and specific manipulation of actin and myosin we found that actin polymerization and myosin contractility are not enough to explain the cells behavior. We show that ever-present depolymerization forces, a direct entropic consequence of actin filament recycling, are sufficient to fill this gap, even under heavy loads.