UC San Diego

Clathrin-mediated endocytosis (CME) is a critical dynamic cellular process that enables membrane trafficking. While electron micrographs have revealed the diver- sity of clathrin lattice shapes, most mechanical models of membrane deformation impose axisymmetric constraints. In this study, we employ a coordinate-free, dis- crete differential geometric framework (Mem3DG) to simulate non-axisymmetric membrane deformations during CME and investigate the mechanical principles governing bud formation. We explore how asymmetries in the clathrin coat geom- etry affect the energy cost of endocytosis and assess the validity of commonly used mechanical models, including the constant area and constant curvature models, in highly asymmetric cases. We anticipate that for small degrees of asymmetry, coat shape may have minimal influence on budding regulation. However, we pre- dict that beyond a critical threshold, asymmetric coats can facilitate energetically favorable bud formation, consistent with experimental observations. Our simula- tions provide new insights into the regulation of CME across different mechanical regimes and offer quantitative predictions for how membrane properties interact with coat geometries to drive endocytic vesicle formation.