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Numerical study of clathrin-mediated endocytosis of nanoparticles by cells under tension

Acta Mechanica Sinica 2019年第3期35卷 691-701页

作者： Xinyue Liu Hongwei Yang Yunqiao Liu Xiaobo Gong Huaxiong Huang Key Laboratory of Hydrodynamics (Ministry of Education) Department of Engineering MechanicsSchool of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Aeronautics and Astronautics Fudan UniversityShanghai 200433China Department of Mathematics and Statistics York UniversityTorontoON M3J 1P3Canada

In this study, a three-dimensional mathematical model was used to study the contribution of clathrins during the process of cellular uptake of spherical nanoparticles under different membrane tensions. The clathrin-coated pit (CCP) that forms around the inward budding of the cell membrane was modeled as a vesicle with bending rigidity. An optimization algorithm was proposed for minimizing the total energy of the system, which comprises the deforming nanoparticle, receptor-ligand bonds, cell membrane, and CCP, in which way, the profile of the system is acquired. The results showed that the CCP enable full wrapping of the nanoparticles at various membrane tensions. When the cell membrane tension increases, the total deformation energy also increases, but the ratio of CCP bending to the minimum value of the total energy of the system decreases. The results also showed that the diameter of the endocytic vesicles determined by the competition between the stretching of the cell membrane and confinement of the coated pits are much larger than the nanoparticles, which is quit different as the results in passive endocytosis that is not facilitated by the CCPs. The present results indicate that variations of tension on cell membranes constitutes a biophysical marker for understanding the size distribution of CCPs observed in experiments. The present results also suggest that the early abortion of endocytosis is related to that the receptor-ligand bonds cannot generate adequate force to wrap the nanoparticles into the cell membrane before the clathrins respond to support the endocytic vesicles. Correspondingly, late abortion may relate to the inability of CCPs to confine the nanoparticles until the occurrence of the necking stage of endocytosis.

关键词： Endocytosis Minimum energy method Membrane tension Clathrin-coated pit receptor-ligand bond

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A Numerical Study of Passive receptor-Mediated Endocytosis of Nanoparticles:The Effect of Mechanical Properties

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Computer Modeling in Engineering & Sciences 2018年第8期116卷 281-300页

作者： Xinyue Liu Yunqiao Liu Xiaobo Gong Huaxiong Huang Key Laboratory of Hydrodynamics(Ministry of Education) Department of Engineering MechanicSchool of Naval ArchitectureOcean and Civil EngineeringShanghai Jiao Tong UniversityShanghai200240China. Department of Mathematics and Statistics York UniversityTorontoOntarioM3J1P3Canada.

In this work,a three-dimensional axisymmetric model with nanoparticle,receptor-ligand bonds and cell membrane as a system was used to study the quasi-static receptor-mediated endocytosis process of spherical nanoparticles in drug *** minimization of the system energy function was carried out numerically,and the deformations of nanoparticle,receptor-ligand bonds and cell membrane were *** show that passive endocytosis may fail due to the rupture of receptor-ligand bonds during the wrapping process,and the size and rigidity of nanoparticles affect the total deformation energy and the terminal wrapping *** results suggest that,in addition to the energy requirement,the success of passive endocytosis also depends on the maximum strength of the receptor-ligand bonds.

关键词： receptor-mediated endocytosis nanoparticle uptake optimization method receptor-ligand bonds drug delivery

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