Mechanics of receptor-mediated endocytosis

Abstract

Most viruses and bioparticles endocytosed by cells have characteristic sizes in the range of tens to hundreds of nanometers. The process of viruses entering and leaving animal cells is mediated by the binding interaction between ligand molecules on the viral capid and their receptor molecules on the cell membrane. How does the size of a bioparticle affect receptor-mediated endocytosis? Here, we study how a cell membrane containing diffusive mobile receptors wraps around a ligand-coated cylindrical or spherical particle. It is shown that particles in the size range of tens to hundreds of nanometers can enter or exit cells via wrapping even in the absence of clathrin or caveolin coats, and an optimal particles size exists for the smallest wrapping time. This model can also be extended to include the effect of clathrin coat. The results seem to show broad agreement with experimental observations. cell adhesion ͉ vesicle budding ͉ virus ͉ biomembrane ͉ receptor-ligand binding R eceptor-mediated endocytosis is one of the most important processes with which viruses and bioparticles can enter or leave an animal cell. Viruses have thousands of different shapes and sizes. Most viruses show a characteristic size in the range of tens to hundreds of nanometers (1, 2). Equipped with a limited amount of nucleic acid, viruses propagate by parasitizing host cells and multiplying their viral nucleic acid and protein capsid via the biochemical machinery of the host. The life cycle of a virus follows a sequential route through various compartments of the host as illustrated in Fig. 1 (3). It takes only 20-40 min for many bacterial phages to finish one life cycle from infection to lysis. For most animal viruses, entering and leaving a host cell are mediated by specific binding of outer coat proteins (such as hemagglutinin in the case of influenza viruses) to specific mobile receptors on the host cell surface.It has been generally assumed that the endocytosis of viruses is associated with the formation of a clathrin coat at the inner membrane leaflet (4). Typically, clathrin coats can generate a membrane radius of curvature as small as Ϸ50 nm. The formation of such small buds has been explained in terms of the bending elasticity concept by considering topological defects of the clathrin network (5). More recently, however, it has been shown that influenza viruses can enter cells even if the formation of clathrin coats are inhibited (6, 7). Here, we develop a model to explain the mechanism of clathrin-free entry of viruses into cells. This model can easily be extended to account for the effect of a clathrin coat.The endocytic pathway is also of interest for understanding possible mechanisms by which nanomaterials might enter into human or animal cells, a significant issue for the development of gene and drug delivery tools (8, 9), as well as for assessing the potential hazard of nanotechnology on ecology and human health (10)(11)(12)(13)(14).Experimental studies on targeted drug delivery into cells have identified particle size as an...

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