纳米颗粒与细胞交互作用中的颗粒尺寸、形状、弹性性能效应研究

Understanding the way cells interact with nanoparticles is important for creating safer biomedical diagnostics and therapies, and for regulating occupational and enviromental exposure. The current project aims to probe the mechanical principles of cell-nanoparticles interactions through experimental, theoretical and molecular dynamics work.The investigations focus on the effect of size,shape,elasticity and density of nanoparticles on the cell uptake.The theoretical model is developed to study the role of interaction of elastic nanoparticles on the cell uptake. The coarse grained molecular dynamics simulations are conducted to study the role of particle size on the fusion of lipid bilayers, with which the new pathway of nanoparticles enter into the vesicle is proposed.The 2-dimensional nanomaterials, such as graphene-family materials, are investigated, focusing on their disruption to the lipid bilayer and the pathways they enter into the cell. A set of effective theories and methods are developed to elucidate the role of particle size,shape,elasticity on the cell uptake, subsequently provide guidelines to the implication of nanomaterials in the biotechnology and nanotechnology.

研究并理解纳米颗粒与细胞的交互作用及其进入细胞途径，对评估纳米材料的生态危害性及其在生物医学诊疗中的安全应用具有重要意义。本项目拟从力学的角度出发，通过实验、分子动力学模拟、理论建模等方法研究纳米颗粒与细胞的交互作用，分析其进入细胞的途径。着重研究颗粒的尺寸、形状、弹性性能对交互作用的影响：建立理论模型研究弹性颗粒间的相互作用对细胞膜包裹颗粒的影响；运用粗粒化的分子动力学模拟研究磷脂双层膜之间的融合受颗粒尺寸的影响，以确定颗粒进入细胞内囊泡的新途径；选取石墨烯为代表研究二维纳米材料对细胞膜的破坏以及进入细胞的多种途径。发展一套有效的理论与方法揭示颗粒进入细胞时对尺寸、形状、弹性性能的依赖性，为纳米材料在生物、纳米科技中的安全使用提供思路与参考。

本项目针对纳米颗粒与细胞交互作用中的关键力学问题开展了深入的实验、理论与模拟研究，取得了若干重要研究进展和创新成果，并归纳了如下主要4点：（1）石墨烯等二维材料进入细胞膜的方式随石墨片尺寸、厚度、表面修饰的影响规律。（2）多个纳米颗粒协同作用进入细胞时的尺寸、形状、间距效应。（3）一维纳米材料进入细胞时的进入角度随材料尺寸、细胞膜内张力、细胞膜刚度的影响规律。（4）颗粒刚度对其进入细胞的影响规律。本项目共在本领域的重要国际、国内学术刊物发表论文15篇。其中SCI论文13篇，EI论文2篇。此外，培养毕业硕士生2人，即将完成博士学位论文1篇，硕士学位论文1篇。另有在读硕士生2人。