Low-intensity pulsed ultrasound (LIPUS) is a clinically used therapy that promotes healing of fractured bones and also improves the healing of other tissues. Nevertheless, only a little is known about its underlying mechanisms of action. In their study on page 2277, Christoph Ballestrem and co-workers investigate how the physical stimulation of cells, through the forces exerted by LIPUS, is converted into biochemical signalling to elicit a wound-healing response. By using live-cell imaging, they observe a dramatic rearrangement of the actin cytoskeleton upon stimulation with LIPUS, including the formation of circular dorsal ruffles and protrusions, resulting in increased cell motility. Mechanistically, the authors show that LIPUS induces the activation of Rac1 and Cdc42, with Rac1 mediating the observed cytoskeletal changes. In addressing the question of how LIPUS is sensed by the cell, the authors demonstrate that mechanosensing is mediated through vinculin at focal adhesions, as disrupting the link between vinculin and the actin cytoskeleton abolished the LIPUS-mediated effects on cell motility. Interestingly, LIPUS also increased the number of EEA1-positive endosomes in a Rac1-dependent manner, which, as shown here, is also dependent on vinculin. This work thus describes a pathway for LIPUS sensing that involves a role for vinculin in modulating a Rab5–Rac1 pathway to stimulate endocytosis and cell motility, thereby contributing to wound healing.
