Theoretical model of efficient phagocytosis driven by curved membrane proteins and active cytoskeleton forces

TL;DR

This paper presents a theoretical model of phagocytosis that explains how curved membrane proteins and active forces facilitate particle engulfment, highlighting the roles of membrane curvature, protein organization, and particle shape.

Contribution

It introduces a coarse-grained model demonstrating how curved proteins and cytoskeletal forces optimize phagocytosis, including effects of particle shape and orientation.

Findings

Curved proteins lower energy cost for engulfment.

Active forces accelerate and reduce protein density needed.

Non-spherical particles are harder to engulf, orientation matters.

Abstract

Phagocytosis is the process of engulfment and internalization of comparatively large particles by the cell, that plays a central role in the functioning of our immune system. We study the process of phagocytosis by considering a simplified coarse grained model of a three-dimensional vesicle, having uniform adhesion interaction with a rigid particle, in the presence of curved membrane proteins and active cytoskeletal forces. Complete engulfment is achieved when the bending energy cost of the vesicle is balanced by the gain in the adhesion energy. The presence of curved (convex) proteins reduces the bending energy cost by self-organizing with higher density at the highly curved leading edge of the engulfing membrane, which forms the circular rim of the phagocytic cup that wraps around the particle. This allows the engulfment to occur at much smaller adhesion strength. When the curved proteins exert outwards protrusive forces, representing actin polymerization, at the leading edge, we find that engulfment is achieved more quickly and at lower protein density. We consider spherical as well as non-spherical particles, and find that non-spherical particles are more difficult to engulf in comparison to the spherical particles of the same surface area. For non-spherical particles, the engulfment time crucially depends upon the initial orientation of the particles with respect to the vesicle. Our model offers a mechanism for the spontaneous self-organization of the actin cytoskeleton at the phagocytic cup, in good agreement with recent high-resolution experimental observations.