Curvature sensing as an emergent property of multiscale assembly of septins

Significance Cells use their membrane curvature to coordinate the activation and spatiotemporal compartmentalization of molecules during key cellular processes. Recent works have identified different proteins that can sense or induce membrane curvature from nanometer to micrometer scale. Septins are nanoscopic cytoskeletal proteins that preferentially bind to membranes with a narrow range of micrometer-scale curvatures. Yet, the sensing mechanism remains ambiguous. Using a combination of microscopy and kinetic modeling, we show that, unlike most proteins that sense curvature in a single protein scale, curvature sensing in septins emerges from their multistep hierarchical assembly on the membrane. This introduces a protein localization scheme where the same protein can be deployed for differential binding sensitivities in different cellular contexts.

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