Fibrillar force generation by fibroblasts depends on formin

Abstract

Fibroblasts in the extra-cellular matrix (ECM) often adopt a predominantly one-dimensional fibrillar geometry by virtue of their adhesion to the fibrils in the ECM. How much forces such fibrillar fibroblasts exert and how they respond to the extended stiffness of their micro-environment comprising of other ECM components and cells are not clear. We use fibroblasts adherent on fibronectin lines micropatterned onto soft polyacrylamide gels as an in vitro experimental model that maintains fibrillar cell morphology while still letting the cell mechanically interact with a continuous micro-environment of specified stiffness. We find that the exerted traction, quantified as the strain energy or the maximum exerted traction stress, is not a function of cell length. Both the strain energy and the maximum traction stress exerted by fibrillar cells are similar for low (13 kPa) or high (45 kPa) micro-environmental stiffness. Furthermore, we find that fibrillar fibroblasts exhibit prominent linear actin structures. Accordingly, inhibition of the formin family of nucleators strongly decreases the exerted traction forces. Interestingly, fibrillar cell migration is, however, not affected under formin inhibition. Our results suggest that fibrillar cell migration in such soft microenvironments is not dependent on high cellular force exertion in the absence of other topological constraints.

Keywords: Actin nucleation; Extra-cellular matrix; Fibrosis; Mechanobiology; Micropatterning; Traction force.