Vesiculation mechanisms mediated by anisotropic proteins

TL;DR

This study uses an extended Helfrich model to explore how anisotropic proteins, like BAR proteins, facilitate vesicle formation by inducing specific membrane curvatures, revealing mechanisms beyond classical isotropic curvature effects.

Contribution

It introduces a theoretical framework showing how anisotropic curvatures generated by proteins influence vesicle formation, expanding understanding beyond traditional models.

Findings

Anisotropic curvatures promote necking and vesicle formation.

Membrane force relationships depend on the type of anisotropic curvature.

Classical Helfrich model cannot explain vesicle fission by spontaneous curvature alone.

Abstract

Endocytosis is an essential biological process for the trafficking of macromolecules (cargo) and membrane proteins in cells. In yeast cells, this involves the invagination of a tubular structure on the membrane and the formation of endocytic vesicles. Bin/Amphiphysin/Rvs (BAR) proteins holding a crescent-shape are generally assumed to be the active player to squeeze the tubular structure and pinch off the vesicle by forming a scaffold on the side of the tubular membrane. Here we use the extended Helfrich model to theoretically investigate how BAR proteins help drive the formation of vesicles via generating anisotropic curvatures. Our results show that, within the classical Helfrich model, increasing the spontaneous curvature at the side of a tubular membrane is unable to reduce the tube radius to a critical size to induce membrane fission. However, membranes coated with proteins that generate anisotropic curvatures are prone to experience an hourglass-shaped necking or a tube-shaped necking process, an important step leading to membrane fission and vesicle formation. In addition, our study shows that depending on the type of anisotropic curvatures generated by a protein, the force to maintain the protein coated membrane at a tubular shape exhibits qualitatively different relationship with the spontaneous curvature. This result provides an experimental guidance to determine the type of anisotropic curvatures of a protein.