树枝状大分子跨细胞双层磷脂膜输运过程及机理的介观模拟及理论分析

项目名称： 树枝状大分子跨细胞双层磷脂膜输运过程及机理的介观模拟及理论分析

项目编号： No.51273105

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 燕立唐

作者单位： 清华大学

项目金额： 80万元

中文摘要： 本项目旨在运用介观模拟方法，研究树枝状大分子（Dendrimer）跨细胞双层磷脂膜输运的动力学过程和路径，并对该过程进行相应的理论分析，以期阐明此类功能纳米粒子细胞内化过程的机理。首先采用耗散粒子动力学方法模拟不同代数的单一带电Dendrimer分子在较大尺寸的磷脂双层膜上组装所形成的结构，并对拉伸和压缩薄膜过程中该体系的曲率能、拓扑能和弹性能等进行理论计算和分析，以阐明膜结构影响下跨膜输运的过程、路径及机理。随后，将粗粒化的受体分子引入双层磷脂薄膜中，探讨受体浓度、受体-Dendrimer相互作用强度等对Dendrimer跨膜输运过程及机理的影响。在此基础上，增加体系中Dendrimer分子的数量，从而深入研究和分析该输运过程中潜在的多Dendrimer协同效应。为探索Dendrimer类型的带电超分子跨膜输运机理及其潜在的细胞毒性，开发新型靶向药物输运体系奠定理论基础，形成原创性成果。

中文关键词： 拓扑大分子；磷脂双层膜；细胞作用；动力学；理论模拟

英文摘要： Understanding the interactions of nanoparticles with biological membranes is of fundamental importance in determining their potential application as drug delivery vehicles and therapeutic agents. As a framework in multifunctional nanodevices, dendrimers are particularly useful in the development of targeted chemotherapeutic agents. To understand the dynamical process and mechanisms of the transmembrane transport of dendrimers however requires direct measurements in a single cell and is thereby very difficult and more challenging. Tailored computer simulations offer a unique approach to address these unresolved issues through identifying and separating individual contributions to the phenomenon. In this project, the dynamical process and mechanisms during the internalization of dendrimers across a lipid bilayer membrane are investigated by employing systematically mesoscopic simulations and theoretical analysis. Firstly, the self-assembly of a single dendrimer on a bilayer membrane patch with large size will be studied by dissipative particle dynamics, where the effects of dendrimer generation and electrostatic interaction on the internalization approaches, including uptake, penetration and membrane damage, of the dendrimer will be investigated. The membrane will also be stretched or compressed to examine the sur

英文关键词： Topological macromolecules；Lipid bilayer membrane；Cellular intereaction；Dynamics；Theory and simulation