功能性纳米颗粒对生物膜表面重构的物理效应研究

Nanoparticles are widely used in medicines, food and cosmetic additives.Nanoparticls can enter into cells by endocytosis or directly penetrating through the cell membrane. However the interactions between nanoparticles and bio-memberane are difficalt to study,due to the complexity of the bio-membranes, the diversity of nanoparticles and the lack in situ analytical methods. Until now we can not explain the detailed phasic changes and reconstructions of the bioligical membranes, during the nanoparticles penetrat progress. This project will use Sum Frequency Generation spectroscopy (SFG) to study the molecular interaction between bio-memberane and nanoparticles.By using SFG, we can elucidate the physical changes of bio-membrane while interacting with nanoparticles at the molecular level. The particles with different structurs,different surface functional groups and different diameters will be investigate. Based on the SFG research we will understand the physicle principle on interacitons of different type of nanoparticle with different bio-memberane. SFG has monolayer sensitivity and can be used for in situ study on biotic/abiotic interfaces. ATR-FTIR, confocal microscopy and other techniques will also be used to study interactions between nanoparticles and biological membranes, to suppliment the SFG results. This research will develop a new method to systematically study the physical effect of interactions between nanoparticles and biological membrances at the molecular level. This study will have a potential for synthesize guidance and performance design of nanoparticles.

纳米颗粒被广泛用于药品、食品及化妆品辅料，与生物体作用时它们可能被吞噬或穿过生物膜。由于生物膜的复杂性、纳米材料的多样性及原位研究界面手段的缺乏，纳米颗粒如何通过生物膜及该过程中生物膜的重构等物理变化尚未明确。本项目拟利用和频振动光谱(SFG)研究纳米颗粒对模拟生物膜-磷脂双层膜的影响，从分子层面描述不同结构纳米颗粒在与生物膜接触时膜表面结构发生物理变化的规律。研究将系统考察不同尺寸、不同表面电荷密度和官能团的纳米颗粒与不同构成的磷脂双层膜间的作用关系。SFG具有单分子层的灵敏度，并且能够原位研究生物-非生物界面。同时全反射红外、荧光共聚焦显微镜等仪器也会被用于纳米颗粒与生物膜的研究, 为SFG结果提供支持。此课题将发展在分子层面系统研究纳米颗粒与生物膜相关物理作用的手段，为未来研究纳米颗粒在其他生物界面的分子作用机制提供方法,为功能性纳米颗粒的结构设计、性能研究和制备方法提供方案。

研究首先设计了具有不同表面官能团的颗粒材料，并且构建了磷脂双层膜体系，利用荧光发光及激光共聚焦荧光显微镜等手段检测了不同纳米颗粒对不同磷脂膜的破坏过程，利用SFG检测了不同表面官能团的纳米颗粒所引发的磷脂双层膜偏转及变构，研究了用于SFG的相关基底高分子及其制备方法，同时按照计划内容探索了细胞与纳米颗粒相互作用的相关过程，并且与SFG实验对照观察，最终发现纳米材料大小对其进入细胞膜的速度和方式有决定性影响，粒径较大的纳米颗粒材料相比较于小粒径的纳米颗粒更难以通过直接改变磷脂膜结构而进入细胞；材料的亲水性会引起材料与细胞磷脂双层膜结构的强烈响应；纳米材料表面的官能团对材料的跨膜递送及相关结构影响并不强烈，同时发现，颗粒表面蛋白冠（冕）对颗粒在生物体系中的相关作用影响较大，而蛋白冠的有效性同时也受到颗粒本身官能团和颗粒大小等相关性质的影响。