Lipid bilayer-inorganic nanoparticle interactions: Model systems to examine the role of particle size and surface chemistry on cell membrane stability

随着基于纳米材料的商业技术和产品的出现，重要的是要同时进行研究，以评估它们对健康和环境的潜在影响。生物膜定义了细胞的结构和功能，并提供了细胞/纳米材料相互作用的初始接触点。然而，在体外或体内研究中，量化这些相互作用并将其与纳米材料的生物相容性联系起来已被证明是困难的。本项目将研究脂质双分子层的热力学和运输特性，作为模型膜，暴露于工程纳米颗粒中。目的是通过阐明特定的双层/纳米颗粒相互作用机制，确定纳米颗粒组成、大小和表面化学对生物膜稳定性的影响。直接感兴趣的材料包括碳富勒烯，天然或疏水改性氧化铝，氧化铁和银纳米颗粒，范围从5到20纳米。研究将在四个具体目标下进行：(1)将开发使用囊泡和支撑脂质膜（SLMs，平面）形式的模型脂质双层来检查生物膜-纳米颗粒相互作用的协议。将从两个几何图形中获得补充信息。(2)表征生物膜对纳米粒子响应的热力学性质变化，如相行为和熔融协同性。这包括纳米颗粒在双分子层内（疏水）或在脂/水界面（亲水）的吸附。(3)被吸附的纳米颗粒改变双分子层内脂质横向扩散的能力，这与细胞膜的动态行为有关，将被研究。(4)通过吸附纳米颗粒的双层稳定和/或不稳定作用来改变跨膜通透性将被表征。纳米材料的毒性近年来受到了相当大的关注，本项目研究了与细胞膜和纳米颗粒生物积累有关的一个特定方面。了解这种相互作用将有助于设计生物相容性纳米材料。除了出版物和演讲外，他们还将在他们的研究网站和NIOSH纳米粒子信息库网站上传播他们的研究结果。此外，形成的新结构将提供有趣的混合脂质体系统，可能用于医疗和制药领域。该项目还将作为高中、本科生和研究生的教育工具。PI参加了一个暑期高中实习项目，并与新英格兰LSAMP项目联系，指导学生。这些项目针对的是工程专业代表性不足的学生。最后，这个项目背后的概念和获得的结果将被用作春季学期开设的跨学科研究生生物纳米技术课程的教材。

CBET- 0828022 BothunAs nanomaterial-based commercial technologies and products emerge, it is important that studies be conducted in tandem to gauge their potential health and environmental impacts. Biological membranes define cell structure and function, and provide an initial point of contact for cell/nanomaterial interactions. However, quantifying these interactions and relating them to nanomaterial biocompatibility has proven difficult using in vitro or in vivo studies. This project will examine thermodynamic and transport properties of lipid bilayers, as model membranes, exposed to engineered nanoparticles. The goal is to determine the effect of nanoparticle composition, size, and surface chemistry on biomembrane stability by elucidating specific bilayer/nanoparticle interactions mechanisms. Materials of immediate interest include carbon fullerenes, and native or hydrophobically modified alumina, iron oxide, and silver nanoparticles ranging from 5 to 20 nm. Research will be conducted under four specific aims: (1) Protocols will be developed for examining biomembrane-nanoparticle interactions using model lipid bilayers in the form of vesicles and supported lipid membranes (SLMs, planar). Complimentary information will be obtained from the two geometries. (2) Changes in thermodynamic properties, such as phase behavior and melting cooperativity, associated with biomembrane response to nanoparticles will be characterized. This includes nanoparticles adsorbing within the bilayer (hydrophobic) or at the lipid/water interface (hydrophilic). (3) The ability of adsorbed nanoparticles to alter the lateral diffusion of lipids within the bilayer, which relates to the dynamic behavior of cell membranes, will be examined. (4) Changes in transmembrane permeability due to bilayer stabilization and/or destabilization with adsorbed nanoparticles will be characterized.Nanomaterial toxicity has received considerable attention as of late, and this project addresses a specific aspect related to the cell membrane and nanoparticle bioaccumulation. Understanding such interactions will aid the design of biocompatible nanomaterials. In addition to publications and presentations, they will disseminate their results on their research website and the NIOSH Nanoparticle Information Library website. In addition, the new structures formed will provide interesting hybrid liposomal systems that could potentially be used in the medical and pharmaceutical fields. This project will also serve as an educational tool for high school, undergraduate, and graduate students. The PI participates in a summer high school intern program and has been contacted by the New England LSAMP program to mentor students. These programs target underrepresented students in engineering. Finally, the concepts behind this project and the results obtained will be used as teaching material in a new interdisciplinary graduate-level Bionanotechnology course offered in the spring semester.