Mechanical Stress-Driven Changes in the Dynamics of Cytoskeletal Proteins

Physical forces drive cell shape across diverse processes such as cytokinesis, cell migration and tissue invasion. The actin cytoskeleton provides the framework for regulating cell shape in response to mechanical stress. In the social amoeba Dictyostelium discoideum, a myosin II-based mechanosensory system controls cellular contractility and cell shape. The IQGAP proteins bind to the actin crosslinker, cortexillin I, and regulate myosin accumulation under stress. To determine how these proteins interact to regulate contractility, we studied the protein dynamics using fluorescence recovery after photobleaching (FRAP). We observe mechanical stress-dependent reduction in the mobility and network release of these proteins from the cytoskeleton. These altered dynamics could reflect a new mechanism for the accumulation of the mechanosensory proteins under stress by local rearrangement of the actin cytoskeleton microstructure. Additionally, IQGAP2 regulates the dynamics of cortexillin I under stress, indicating a functional relevance for the biochemical interaction between these proteins. These studies will help determine how cell shape is regulated various mechanical contexts, which will be valuable for understanding processes such as metastasis and tissue remodeling.