Figure 8 |. Origins of tension heterogeneity across the plasma membrane of spreading and migrating cells.

(a) When newly placed on a substrate, the cell appears rounded and membrane tension is localised at membrane folds, (b) Isotropic spreading occurs as extra membrane is unfolded. Tension rises at locations of actin cytoskeleton polymerisation and as additional area provided by membrane folds is depleted, (c) Anisotropic spreading occurs, where focal adhesions are formed from actin rearrangement. Exocytosis levels increase to balance the high membrane tension manifested in isotropic spreading, (d) Plasma membrane area dramatically increases as the cell reduces the number of protrusions. Focal adhesions attach tightly to the substrate and tension stabilises towards a resting level, as cell spreading completes. Exocytosis activity is balanced by CME, which experiences spatlotemporal heterogeneity upon spreading, (e) Cell polarisation occurs due to rearrangement of the actin cytoskeleton, which results in the generation of a single stable protrusion at the leading edge and multiple protrusions at the trailing edge. A front-to-rear tension heterogeneity in the plasma membrane Is exhibited [Lieber et al., 2015], where CME activity is reduced at the leading edge and enhanced at the trailing edge [Willy et al., 2017]. (f) Cell polarity is improved by adhesive contacts between the cell and the substrate. The establishment of a front-to-rear tension gradient generated by cell polarisation induces migration to occur.