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

CBET-0828022随着基于纳米材料的商业技术和产品的出现，重要的是同时进行研究，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，并为细胞/纳米材料的相互作用提供了一个初始接触点。然而，利用体外或体内研究证明，量化这些相互作用并将它们与纳米材料的生物相容性联系起来是困难的。该项目将研究暴露在工程纳米颗粒中的脂类双层作为模型膜的热力学和传输特性。其目的是通过阐明特定的双层/纳米颗粒相互作用机制来确定纳米颗粒的组成、尺寸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、天然或疏水修饰的氧化铝、氧化铁和纳米银颗粒，范围从5到20纳米。研究将在四个具体目标下进行：(1)将制定使用囊泡和支撑脂膜(SLM，平面)形式的模型脂双层检查生物膜-纳米颗粒相互作用的方案。我们将从这两个几何图形中获得补充信息。(2)将表征与生物膜对纳米颗粒的响应相关的热力学性质的变化，例如相行为和熔融协同性。这包括吸附在双层(疏水性)或脂/水界面(亲水性)的纳米颗粒。(3)将考察吸附纳米颗粒改变双层内脂类横向扩散的能力，这与细胞膜的动态行为有关。(4)由于吸附的纳米颗粒的双层稳定和/或失稳引起的跨膜通透性的变化将被表征。纳米材料的毒性最近受到了相当大的关注，这个项目解决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生物兼容纳米材料的设计。除了出版物和演示文稿外，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成果。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生计划，并已与新英格兰LSAMP计划联系，以指导学生。这些项目针对的是工程学专业中代表性不足的学生。最后，这个项目背后的概念和所获得的结果将被用作春季学期开设的一门新的跨学科研究生水平的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.