Stochastic simulations of nanoparticle internalization through transferrin receptor dependent clathrin-mediated endocytosis. 2018

Hua Deng, and Prashanta Dutta, and Jin Liu
School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164-2920, United States.

Receptor dependent clathrin-mediated endocytosis (CME) is one of the most important endocytic pathways for the internalization of bioparticles into cells. During CME, the ligand-receptor interactions, development of clathrin-coated pit (CCP) and membrane evolution all act together to drive the internalization of bioparticles. In this work, we develop a stochastic computational model to investigate the CME based on the Metropolis Monte Carlo simulations. The model is based on the combination of a stochastic particle binding model with a membrane model. The energetic costs of membrane bending, CCP formation and ligand-receptor interactions are systematically linked together. We implement our model to investigate the effects of particle size, ligand density and membrane stiffness on the overall process of CME from the drug delivery perspectives. Consistent with some experiments, our results show that the intermediate particle size and ligand density favor the particle internalization. Moreover, our results show that it is easier for a particle to enter a cell with softer membrane. The model presented here is able to provide mechanistic insights into CME and can be readily modified to include other important factors, such as actins. The predictions from the model will aid in the therapeutic design of intracellular/transcellular drug delivery and antiviral interventions.

UI MeSH Term Description Entries
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D011990 Receptors, Transferrin Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released. Transferrin Receptors,Transferrin Receptor,Receptor, Transferrin
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002966 Clathrin The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D053758 Nanoparticles Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging. Nanocrystalline Materials,Nanocrystals,Material, Nanocrystalline,Materials, Nanocrystalline,Nanocrystal,Nanocrystalline Material,Nanoparticle
D022163 Clathrin-Coated Vesicles Vesicles formed when cell-membrane coated pits (COATED PITS, CELL-MEMBRANE) invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of the protein CLATHRIN. Shortly after formation, however, the clathrin coat is removed and the vesicles are referred to as ENDOSOMES. Clathrin Coated Vesicles,Clathrin-Coated Vesicle,Vesicle, Clathrin-Coated,Vesicles, Clathrin-Coated

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