Engulfment of particles by vesicles containing curved membrane proteins coupled with active cytoskeletal forces

Cells engulf larger particles as a part of the immune response, and also during nutrient uptake, drug delivery and pathogen invasion, via the process known as "phagocytosis". In this chapter, we discuss the mechanism of phagocytosis by considering a simplified coarse grained model of a three-dimensional vesicle, having uniform adhesion interaction with a rigid particle, and containing curved membrane-bound protein complexes (CMC), which in turn recruit 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 convex CMC 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 reduced adhesion strength. When the CMC locally recruits actin polymerization that exerts outward forces on the membrane, we find that engulfment is achieved more quickly and at a lower density of CMC. We consider both spherical as well as non-spherical particles (spheroids, spherocylinders, dumb-bell etc.), 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.