受体介导的二维纳米粒子跨细胞膜输运的模拟及理论研究
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- 英文论文题名：Receptor-Mediated Endocytosis of Two-Dimensional Nanoparticles:Simulation and Theory
- 论文作者：陈鹏宇 ; 黄子涵 ; 燕立唐
- 英文论文作者：Pengyu Chen ; Zihan Huang ; Li-Tang Yan ; Department of Chemical Engineering ; Tsinghua University
- 年：2016
- 作者机构：清华大学化学工程系高分子研究所;
- 论文关键词：受体介导 ; 二维纳米材料 ; 跨膜运输 ; 计算机模拟 ; 理论分析
- 会议召开时间：2016-08-25
- 会议录名称：中国化学会2016年软物质理论计算与模拟会议论文摘要集
- 语种：中文
- 分类号：R318;TB383.1
- 学会代码：ZGHY
- 会议名称：中国化学会2016年软物质理论计算与模拟会议
- 会议地点：中国天津
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：2
- 文件大小：185k
- 原文格式：D
- 会议级别：全国
摘要
二维纳米粒子因具有特殊的拓扑结构及独特的性能,可能作为新型的纳米载体用于疾病的诊断和治疗。因此,研究二维纳米粒子跨细胞膜输运的动力学路径及机理,进而明晰其细胞毒性显得尤为重要。已有实验证明,二维纳米粒子进入细胞膜是受体介导的内吞过程。然而,囿于极短时间尺度和极小的空间尺度,实验难以明晰其详细的跨膜路径及机理,计算机模拟及基于膜弹性理论的理论分析成为洞悉该过程的有效途径。[1-5]因此,本文采用计算机模拟与理论分析相结合的方法,开展了受体介导的二维纳米粒子跨细胞膜输运的模拟与理论研究工作。本文使用介尺度模拟方法,揭示了石墨烯及其衍生物的跨膜输运路径及机理对于细胞膜张力、石墨烯尺寸和受体密度的依赖性。模拟结果表明,改变膜张力和石墨烯尺寸,石墨烯与膜作用可形成多种独特形态,例如:半球胶束结构、三明治结构、刺穿结构、不完全包覆结构及完全包覆结构等。同时,通过模拟与定量的表征,揭示石墨烯跨膜输运过程受到了细胞膜及其独特的自旋转的双重影响。进而,发展了基于膜弹性的Canham-Helfrich理论,对石墨烯跨膜输运过程的能量变化进行了详细的计算和理论分析,阐明了不同形态形成的难易程度,并推导出完全包覆结构的形成由一个无量纲的参数和一个定义明确的关系式主导。该研究详细地阐述了石墨烯跨膜输运的机理及动力学路径,加深了二维纳米粒子跨膜输运动力学及其毒性机理的认识,进而为新型纳米材料的纳米医学应用提供了理论指导。
Two-dimensional nanomaterials,such as graphene and transitional metal dichalcogenide nanosheets,are promising materials for the development of antimicrobial surfaces and the nanocarriers for intracellular therapy.Understanding cell interaction with these emerging materials is an urgent-important issue to promoting their wide applications.Experimental studies suggest that two-dimensional nanomaterials enter cells mainly through receptor-mediated endocytosis.However,the detailed molecular mechanisms and kinetic pathways of such processes remain unknown.Here,we combine computer simulations and theoretical derivation of the energy within the system to show that the receptor-mediated transport of two-dimensional nanomaterials,such as graphene nanosheet across model lipid membrane,experiences a flat vesiculation event governed by the receptor density and membrane tension.The graphene nanosheet is found to undergo revolution relative to the membrane and,particularly,unique self-rotation around its normal during membrane wrapping.We derive explicit expressions for the formation of the flat vesiculation,which reveals that the flat vesiculation event can be fundamentally dominated by a dimensionless parameter and a defined relationship determined by complicated energy contributions.The mechanism offers an essential understanding on the cellular internalization and cytotoxicity of the emerging two-dimensional nanomaterials.
Two-dimensional nanomaterials,such as graphene and transitional metal dichalcogenide nanosheets,are promising materials for the development of antimicrobial surfaces and the nanocarriers for intracellular therapy.Understanding cell interaction with these emerging materials is an urgent-important issue to promoting their wide applications.Experimental studies suggest that two-dimensional nanomaterials enter cells mainly through receptor-mediated endocytosis.However,the detailed molecular mechanisms and kinetic pathways of such processes remain unknown.Here,we combine computer simulations and theoretical derivation of the energy within the system to show that the receptor-mediated transport of two-dimensional nanomaterials,such as graphene nanosheet across model lipid membrane,experiences a flat vesiculation event governed by the receptor density and membrane tension.The graphene nanosheet is found to undergo revolution relative to the membrane and,particularly,unique self-rotation around its normal during membrane wrapping.We derive explicit expressions for the formation of the flat vesiculation,which reveals that the flat vesiculation event can be fundamentally dominated by a dimensionless parameter and a defined relationship determined by complicated energy contributions.The mechanism offers an essential understanding on the cellular internalization and cytotoxicity of the emerging two-dimensional nanomaterials.
引文
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[5]Guo,R.;Mao,J.;Yan,L.T.*ACS Nano 2013,7:10646.
[2]Mao,J.;Guo,R.;Yan,L.T.*Biomaterials 2014,35:6069.
[3]Guo,R.;Mao,J.;Yan,L.T.*Biomaterials 2013,34:4296.
[4]Liang,J.;Chen,P.;Dong,B.;Huang,Z.;Yan,L.T.*Biomacromolecules 2016,17:1834.
[5]Guo,R.;Mao,J.;Yan,L.T.*ACS Nano 2013,7:10646.