Energetics and Stability of Neck Formation in Yeast and Mammalian Endocytosis

Abstract

The formation and constriction of membrane necks is a fundamental step that immediately precedes fission in membrane remodeling processes like endocytosis, viral egress, and cytokinesis. Even in endocytosis, the formations of invaginations and buds are different in yeast vs mammalian cells. In mammalian cells, structural and biophysical studies have identified that constriction of the neck by dynamin helices triggers membrane fission. However, yeast cells do not have dynamin. A detailed physical understanding of the force and energetic requirements for neck constriction in yeast vs mammalian cells is difficult to ascertain using experimental techniques due to the small length scales nearing self contact. In this work, we apply a modified Helfrich theory of lipid membranes to investigate membrane necking in yeast and mammalian endocytosis. Specifically, we seek to understand how applied forces and protein-induced spontaneous curvature contribute to induce necking and energy distribution on the membrane. Application of a radial constricting force, mimicking the action of dynamin, leads to a snapthrough instability in the shape of the membrane during budding. We observe a large energy barrier that can be overcome by force to achieve a narrow neck. This instability is eliminated by applying a region of spontaneous curvature, contracting the radius or widening the force. Application of a pulling force, essential to yeast endocytosis, also leads to snapthrough instability for a rigid protein coat. Here, the instability is eliminated by ensuring uniform rigidity of coat and membrane. We extend the analysis to images of clathrin coated buds from mammalian and yeast experiments and track the process of neck formation. To do this, we implement an image processing framework that was recently implemented by the authors. Our model sheds insight into the defining characteristics of membrane necking and related snapthrough instabilities.