CELL SURFACE RESPONSE TO AN EXTERNAL POINT FORCE: DYNAMIC REMODELING OF THE ACTIN CORTEX

To perform their functions, cells need to interact both biochemically and mechanically with their surroundings. When these interactions are well-coordinated, tissues, organs, and complex organisms like humans are formed. However, if these processes become deregulated, diseases can occur. While there has been significant progress in understanding the biochemical signals that regulate these interactions, the mechanical aspects are less understood.

In mammalian cells, the cell surface, which consists of the plasma membrane and the cortical cytoskeleton, is the primary region that detects and responds to external forces. The biological membrane is made up of lipids and proteins, while the cortical cytoskeleton is mainly composed of actin filaments, myosin and accessory proteins.

In this study, by applying external point forces to different cell surfaces using membrane tether extractions with optical tweezers, we dynamically mapped structural and mechanical responses of the actin cortex. We showed that ceasing external forces immediately after tether formation caused its swift recoil, whereas a 5-minute force application increased tether stiffness and delayed recoil. Such behaviors correlated not only with time-dependent and universal increases in F-actin within tethers across various cell types but also with mechanical changes in tether curves, shifting from steady-state plateaus to frequent spikes in force. The generated tubes appeared fully integrated to cell surfaces, were able to nucleate newly cell surface protrusions, and exhibited dynamic movement. Our findings support a mechano-structural adaptation mechanism where cell surfaces universally respond to external point forces through time-dependent cytoskeleton recruitment. Implications for cell surface reorganization into tubular structures can be further explored.