Mechanics And Dynamics Of Cell Adhesion

Osteoclasts are large, multinucleated cells, which resorb mineralized bone. When an osteoclast encounters a substrate, dot-like actin-rich structures, the podosomes, ap-pear and assemble into clusters, rings or a belt. We experimentally investigate, from a cell population to a single podosome, their function and dynamics. Over a cell popula-tion, kinetic measurements show that the cell surface area A scales as A～K2, where K is the number of nuclei, indicating a flat morphology. By defining quantities that account for the spatial distribution of the actin within the cell, we demonstrate that the podosomes organization only depends on the time after differentiation, and not on K. In a single osteoclast, the observation of a strong coupling between cell spreading and podosomes formation lead us to propose that podosomes play an important role in osteoclast motility. Analysis of osteoclast migration, and the forces it applies on the substrate, demonstrates that the internal dynamics of the actin within the cell does not only correlate with cell migration, but drives it. Finally, in order to under-stand the internal dynamics of a single podosome, we improved the model of Biben et al. (2005) by considering on the one hand, actin polymerization, and on the other hand, diffusion and attachment kinetics of the gelsolin, an actin severing protein. We find that podosomes are mainly governed by the actin dynamics, regardless of gelsolin concentration.