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bioRxiv · 10.64898/2026.03.05.709932

Clathrin is an Intrinsic Driver of Membrane Fission

Bouzos, N.·Foley, S. L.·Potamianos, A.·Jacobs, C. O.·Johnson, M. E.·Zeno, W. F.
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Abstract

Clathrin-mediated endocytosis is a primary internalization pathway where adaptor proteins recruit clathrin and bend the plasma membrane to form clathrin coated vesicles. Since clathrin does not bind membranes directly, its contributions to membrane remodeling remain unclear. Using an in vitro system that recruits clathrin directly to lipid membranes, we show that clathrin alone can drive end-to-end membrane budding and vesicle fission. Surprisingly, stronger clathrin assembly (i.e., higher membrane association) yields weaker membrane fission, indicating that membrane remodeling depends not simply on how much clathrin is recruited, but on how the resulting lattice is assembled. Brownian dynamics simulations, together with experimentally measured shifts in clathrin cage diameter, suggest that this counterintuitive behavior arises at least in part from assembly-dependent changes in intrinsic lattice curvature. This framework extends to adaptor-mediated recruitment, with clathrin either assisting or opposing membrane fission in an adaptor-dependent manner. Together, these findings support a mechanism by which coat protein mechanics regulate membrane remodeling.

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Bouzos, N., Foley, S. L., Potamianos, A., Jacobs, C. O., Johnson, M. E., Zeno, W. F.. 2026-03-06. Clathrin is an Intrinsic Driver of Membrane Fission. https://doi.org/10.64898/2026.03.05.709932

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