Modeling receptor-mediated endocytosis via mechanics of cell adhesion
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Modeling receptor-mediated endocytosis via mechanics of cell adhesion W. Shi1, 2, H. Gao1, L. B. Freund3 Max Planck Institute for Metals Research, Heisenbergstrasse 3, D-70569 Stuttgart, Germany. 2 Department of Engineering Mechanics, Tsinghua University, Beijing 100084, P.R. China. 3 Division of Engineering, Brown University, Providence, RI 02912, USA 1
ABSTRACT A mathematical model describing how a cell membrane with diffusive mobile receptors wraps around a ligand coated cylindrical or spherical particle has been recently developed to model particle size effects in receptor mediated endocytosis. The model predicted an optimal particle size for the smallest wrapping time, as well as a minimum and a maximum particle size for successful wrapping. The results showed that particles in the size range of tens to hundreds of nanometers can enter cells even in the absence of clathrin or caveolin coats. Here we report some further progresses on modeling a spontaneous membrane curvature induced by clathrin or caveolin coats at the inner membrane leaflet as well as simultaneous entry of many particles into cells. It is found that a spontaneous membrane curvature narrows the particle size range for successful wrapping and there exists an optimal particle density for maximum particle adsorptivity. INTRODUCTION We have been studying the size effects in receptor-mediated endocytosis based on the mechanics of cell adhesion [1]. The objective of this research is to understand mechanisms by which nanomaterials might enter into human or animal cells, a significant issue for the development of gene and drug delivery tools [2, 3] as well as for assessing the potential hazard of nanotechnology on ecology and human health [4–9]. One example is carbon nanotubes which have recently been explored as molecular transporters. It has been shown that carbon nanotubes can enter animal cells without apparent toxicity [4–7]. Receptor mediated endocytosis is an essential pathway by which many viruses and bioparticles enter and leave eukaryotic cells. Viruses have thousands of different shapes and sizes. Most of them show a characteristic size in the range of tens to hundreds of nanometers [10, 11]. The life cycle of many viruses follows a sequential route through various compartments of the host as illustrated in figure 1A [12]. The receptor-bound viruses enter and leave animal cells via binding interaction between ligand molecules on the viral capsid and their receptor molecules on the cell membrane, which causes the membrane to wrap around the viral particle. Some enveloped viruses are transported in the intracellular compartments via similar wrapping processes shown in figure 1B [13]. It has been generally assumed that the endocytosis of viruses is assisted by clathrin or caveolin coats formed at the inner membrane leaflet [14]. More recently, however, it has been found that influenza viruses can enter cells even if the formation of clathrin coats are inhibited [15, 16], suggesting that virus can enter or exit cells even
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