Mechanically Induced Conformational Transition of Spectrin in the Mammalian Cell Cortex

Membrane-associated scaffolds (MAS) are the primary determinants in the organization of mesoscale cortical territories during mechanosensation and mechanoadaptation of cells, and are continuously remodeled as a function of intra- and extra-cellular cues. However, the topologies of these MAS and how they transition from one configuration to another are poorly understood. Among MAS, the ubiquitous spectrin meshwork has been described in two distinct conformations that point to different mechanical and cellular properties: the erythroid-specific hexagonal lattice and the neuron-specific periodic array. By combining Expansion Microscopy, biophysical measurements and in silico modelling, we found that both configurations can coexist in the fibroblast cortex. The periodic arrangement is found in small condensates between the stress fibers deep in the cell body, while in the rest of the cortex spectrin appears diffuse. The two conformations can be mechanically and pharmacologically tuned by targeting the actomyosin cytoskeleton, and FRET-tension measurements suggest that spectrin condensates experience less mechanical stress. Our study sheds light on the universal mechanoadaptative properties of the spectrin meshwork, which can create discrete cortical territories by switching between two different periodic conformations.