细胞膜上的纳米颗粒关联动力学研究

It is of great significance for applications of nanoparticles in bio-sensing and nanomedicine to investigate the dynamics of nanoparticles on cellular membrane. Related researches has attracted considerable attention in the field of nanotechnology. Though there are many studies on nanoparticles' self-diffusion dynamics, scholars have little knowledge about the correlated diffusion dynamics of nanoparticles which needs further investigations. In this project, on the basis of molecular dynamics simulations together with the related biophysical theory and the techniques of optical microscopy and particle tracking, we will investigate the correlated dynamics of nanoparticles on cellular membranes and its physical mechanism behind. The research consists of four parts: I) We will explore the changes of the correlated dynamics of particles whose diameter varies from micrometer to nanometer on cellular membrane. II）We will systematically study the correlated dynamics of nanoparticles with three kinds of dimension (nanotube, nanosheets and nanospheres with one, two and three dimension, respectively) at different interaction models (horizontal adsorption and longitudinal penetration) on cellular membrane. III) We will study the influence of cellular membrane and membrane’s sub-domain (such as the raft) on the correlated diffusion of nanoparticles. IV) We will investigate the relationship of the correlated diffusion with membrane’s viscoelasticity and nano-toxicity. This research would be helpful to better understand the novel physics at the nano-biointerface, and provides practical guidance for the design of nano-detectors and nano-drugs.

研究纳米颗粒在细胞膜上的动力学行为，对纳米颗粒在生物传感、纳米医药等方面的应用有重要意义。相关研究业已成为纳米科技领域的前沿热点之一。之前的相关研究更多关注的是纳米颗粒的自扩散动力学，人们对纳米颗粒间的关联扩散动力学了解甚少，有待系统深入的研究。本项目拟采用分子动力学模拟、显微成像和多粒子追踪技术，结合膜的生物物理理论，深入研究纳米颗粒在细胞膜上的关联动力学行为及其背后的物理机制。研究内容包括：1）研究从微米到纳米尺度，颗粒在脂膜上关联扩散动力学规律的变化；2）研究膜上三种维度（一维纳米管、二维纳米片和三维纳米球）的纳米颗粒在不同作用模式（水平吸附式、垂直穿透式）下的关联扩散动力学；3）研究不同种类的生物膜以及生物膜上的不同结构域对纳米颗粒关联扩散的影响；4）研究纳米颗粒的关联扩散与脂膜的粘弹性及纳米毒性的关系。本项目既有助于人们理解纳米-生物界面上新的物理现象，也可为人们设计纳米探测器件

近年来，纳米材料的生物学效应引起了人们的广泛关注。纳米颗粒对药物的输运和跨膜的行为都与纳米颗粒在细胞膜上的动力学密切相关。本项目采用分子动力学模拟、显微成像和多粒子追踪技术，研究了颗粒在膜上的关联动力学行为及其背后的物理机制。研究发现磷脂双层膜上的纳米颗粒在近程、中程和远程区有截然不同的关联扩散规律，关联扩散系数在近程区出现振荡、在远程区快速衰减；磷烯和氧化磷烯纳米片能插入细胞膜并破坏性地抽取磷脂分子进而减弱细胞的活性，被抽取的磷脂分子沿磷烯表面褶皱方向定向排列，小尺寸磷烯纳米片沿特定方向插入细胞膜；纳米颗粒在脂膜上的速度自关联函数出现负关联，随着颗粒尺寸的增大，速度自关联的衰减减慢；不同维度的纳米颗粒在脂膜内的旋转自关联函数有显著的差异，二维纳米片的旋转自关联最强衰减最慢，三维纳米球的旋转自关联最弱衰减最快，一维纳米管介于两者之间；类膜界面附近的颗粒在径向和横向的特征长度各向异性，研究给出了界面附近颗粒的关联标度律及膜的粘度。这些发现有助于人们深入的认识颗粒在膜上的动力学规律，可以为纳米颗粒在生物医药和生物传感领域的应用提供参考。