Effects of nanoparticle size and shape in clathrin-mediated endocytosis

Abstract

Nanoparticles have been extensively adopted to deliver therapeutic drug molecules to cells through clathrin-mediated endocytosis (CME). The size and shape of nanoparticles are important factors in the design of a drug delivery system. Both the clathrin coat and actin force induce the bending of the membrane during CME. However, due to the complex coupled effects of size, shape, and surface properties, nanoparticle shape effects are difficult to elucidate through experiments. Herein, we establish a comprehensive framework considering both the actin force and the dynamic assembly of the clathrin coat. To explore the effect of the nanoparticle size and shape on CME, we construct a clathrin coat growth model with actin force feedback. The clathrin coat growth model, nanoparticle internalization efficiency, and transportation efficiency are discussed through numerical analysis. The transportation efficiency is defined by the energy cost of the cell absorbing unit dose target drug. Numerical results illustrate that the proposed clathrin coat growth model is consistent with the actual physiological process, especially for CME considering receptor-mediated effects. The elliptical nanoparticle exhibits higher internalization and transportation efficiencies. A larger nanoparticle has lower internalization efficiency but higher transportation efficiency. Our results demonstrate that the internalization and transportation efficiencies of nanoparticles with an intermediate aspect ratio are higher than those with low or high aspect ratios. Our model provides insight into the intrinsic mechanism of CME and useful guidance for the practical design of the size and shape of nanoparticles for biopharmaceutical research.