Effects of particle shape and receptor properties on clathrin-mediated endocytosis of ligand-coated bioparticles

The membrane wrapping and internalization of ligand-coated bioparticles, such as viruses and drug carriers, through clathrin-mediated endocytosis (CME) are vitally important for intracellular transport. During CME, the shape of the particle and receptor protperties plays important roles in determination of particle-membrane interactions, but much of the previous work has been focused on spherical particles and the receptor properties have been less studied due to the oversimplifications of the models. In this work, we develop and implement a stochastic model to study the CME of particles with different shapes, and investigate the effects of mechanical (receptor flexure), geometrical (receptor length) and biochemical (ligand-receptor cutoff) properties of receptors on CME. Our results show that particles can be internalized through different entry modes depending on the particle shape. The receptor flexural rigidity plays important roles in CME. There is a threshold beyond which particle internalization will not occur. Shorter receptor length and longer ligand-receptor reaction cutoff promote formation of ligand-receptor bonds and facilitate particle internalization. Our model and simulations provide critical mechanistic insights on CME, and represents a powerful platform for guiding the design of nanoparticles for drug delivery applications.