Elasticity of dense actin networks produces nanonewton protrusive forces at macrophage podosomes
Renaud Poincloux (IPBS, Toulouse)
Actin filaments assemble into force-generating systems that play pivotal roles in diverse cellular functions, including cell motility, adhesion, contractility and division. Thermodynamics and in vitro experiments showed that the polymerization of single actin filaments generates forces in the 1-10 pN range. How networks of crosslinked actin filaments, individually generating piconewton forces, are able to produce forces reaching tens of nanonewtons remains unclear. We used in situ cryo-electron tomography to unveil how the nanoscale architecture of macrophage podosomes enables basal membrane protrusion. We show that the sum of the actin polymerization forces at the membrane is not sufficient to explain the protrusive forces generated by podosomes. Quantitative analysis of podosome organization demonstrates that the core is composed of a dense network of bent actin filaments storing elastic energy. Theoretical modelling of the network as a spring-loaded elastic material reveals that it exerts forces of up to tens of nanonewtons, similar to those evaluated experimentally. Thus, taking into account not only the interface with the membrane but also the bulk of the network is crucial to understand force generation by actin machineries. Our integrative approach sheds light on the elastic behavior of dense actin networks and opens new avenues to understand force production inside cells.