Coat stiffening can explain invagination of clathrin-coated membranes

TL;DR

This paper proposes that coat stiffening, driven by cooperative interactions among clathrin molecules, is the main physical mechanism behind membrane invagination during clathrin-mediated endocytosis, supported by a combined data and energetic model.

Contribution

It introduces a new energetic model showing coat stiffening as the key driver of membrane invagination, integrating high-resolution imaging data into a consensus pathway.

Findings

Cooperative curvature model defines a flat-to-curved transition at finite area.

Coat stiffening can explain membrane invagination driven by intrinsic curvature.

Two length scales, patch size and final pit radius, determine the invagination pathway.

Abstract

Clathrin-mediated endocytosis is the main pathway used by eukaryotic cells to take up extracellular material, but the dominant physical mechanisms driving this process are still elusive. Recently several high-resolution imaging techniques have been used on different cell lines to measure the geometrical properties of clathrin-coated pits over their whole lifetime. Here we first show that the combination of all datasets with the recently introduced cooperative curvature model defines a consensus pathway, which is characterized by a flat to-curved transition at finite area, followed by linear growth and subsequent saturation of curvature. We then apply an energetic model for the composite of plasma membrane and clathrin coat to this consensus pathway to show that the dominant mechanism for invagination could be coat stiffening, which might originate from cooperative interactions between the different clathrin molecules and progressively drives the system towards its intrinsic curvature. Our theory predicts that two length scales determine the invagination pathway, namely the patch size at which the flat-to-curved transition occurs and the final pit radius.