Endocytic proteins drive vesicle growth via instability in high membrane tension environment

TL;DR

This study uncovers how actin and BAR proteins induce a shape transition in membrane vesicles under high tension, revealing mechanisms of vesicle formation and scission in endocytosis.

Contribution

It introduces a new mechanistic model showing actin-driven snap-through instability and BAR protein stabilization in vesicle formation under high membrane tension.

Findings

Actin induces a snap-through instability causing rapid vesicle shape change.

BAR proteins stabilize vesicles and modulate instability.

BAR depolymerization promotes vesicle elongation and scission.

Abstract

Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membrane vesicles. It plays an integral role in nutrient import, signal transduction, neurotransmission and cellular entry of pathogens and drug-carrying nanoparticles. As CME entails substantial local remodeling of the plasma membrane, the presence of membrane tension offers resistance to bending and hence, vesicle formation. Experiments show that in such high tension conditions, actin dynamics is required to carry out CME successfully. In this study, we build upon these pioneering experimental studies to provide fundamental mechanistic insights into the roles of two key endocytic proteins, namely, actin and BAR proteins in driving vesicle formation in high membrane tension environment. Our study reveals a new actin force induced `snap-through instability' that triggers a rapid shape transition from a shallow invagination to a highly invaginated tubular structure. We show that the association of BAR proteins stabilizes vesicles and induces a milder instability. In addition, we present a new counterintuitive role of BAR depolymerization in regulating the shape evolution of vesicles. We show that the dissociation of BAR proteins, supported by actin-BAR synergy, leads to considerable elongation and squeezing of vesicles. Going beyond the membrane geometry, we put forth a new stress-based perspective for the onset of vesicle scission and predict the shapes and composition of detached vesicles. We present the snap-through transition and the high in-plane stress as possible explanations for the intriguing direct transformation of broad and shallow invaginations into detached vesicles in BAR mutant yeast cells.