Mechanically induced topological transition of spectrin regulates its distribution in the mammalian cortex

The cell cortex is a dynamic assembly that ensures cell integrity during passive deformation or active response by adapting cytoskeleton topologies with poorly understood mechanisms. The spectrin meshwork ensures such adaptation in erythrocytes and neurons. Erythrocytes rely on triangular-like lattices of spectrin tetramers, which in neurons are organized in periodic arrays. We exploited Expansion Microscopy to discover that these two distinct topologies can co-exist in other mammalian cells such as fibroblasts. We show through biophysical measurements and computational modeling that spectrin provides coverage of the cortex and, with the intervention of actomyosin, erythroid-like lattices can dynamically transition into condensates resembling neuron-like periodic arrays fenced by actin stress fibers. Spectrin condensates experience lower mechanical stress and turnover despite displaying an extension close to the contour length of the tetramer. Our study sheds light on the adaptive properties of spectrin, which ensures protection of the cortex by undergoing mechanically induced topological transitions.