摘要
研究具有复杂拓扑结构的功能纳米粒子夸细胞膜输运的动力学路径及机理对于明晰其细胞毒性,进而研制新型高效靶向药物输运体系来说具有重要的理论和实际意义。然而,囿于极小的空间尺度和极短的时间尺度,很难单纯通过实验研究来解决此问题。计算机模拟和基于膜弹性理论的理论分析方法因而成为洞悉该过程的有效途径。针对此问题,本课题组采用介尺度模拟和理论分析相结合的方法,开展了对树枝状大分子和两维石墨烯纳米片跨细胞膜输运的计算机模拟和理论分析。[1-5]本论文即集中介绍我们在石墨烯及其衍生物跨细胞膜输运的动力学路径及机理方面的一些理论和模拟研究工作,着重强调其跨膜输运过程的路径和机理对于膜张力,石墨烯尺寸和氧化程度以及膜的受体蛋白等因素的依赖性。通过运用介尺度计算机模拟,我们揭示了石墨烯纳米片与膜作用时的多种独特状态,例如:三明治结构,半球胶束结构,刺穿结构以及膜受体介导的石墨烯表面膜滑移结构等;同时借助基于膜弹性的Canham-Helfrich理论对该过程中的能量变化进行了详细计算和理论分析,阐明了这些不同的状态所对应的跨膜输运动力学路径及其发生的难易程度。最近,通过系统的计算机模拟和理论分析,我们进一步阐述了膜受体蛋白对于石墨烯二维纳米片跨膜输运的影响,发现了一些比较新奇的现象。这些工作对于揭示石墨烯等两维纳米材料潜在的细胞毒性,进而理解其对人体健康的危害性,以及在纳米医学等领域的深入应用具有比较重要的促进作用。
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
[1]Mao,J.;Chen,P.;Liang,J.;Guo,R.;Yan,L.T.*ACS Nano 2016,10:1493.
[2]Liang,J.;Chen,P.;Dong,B.;Huang,Z.;Yan,L.T.*Biomacromolecules 2016,17:1834.
[3]Mao,J.;Guo,R.;Yan,L.T.*Biomaterials 2014,35:6069.
[4]Guo,R.;Mao,J.;Yan,L.T.*ACS Nano 2013,7:10646.
[5]Guo,R.;Mao,J.;Yan,L.T.*Biomaterials 2013,34:4296.
