Correlating Nanoparticle-Induced Biomembrane Perturbation with Heterogeneous Surface Chemistry

工程纳米颗粒(直径在几十纳米量级的无机物颗粒)已经进入了从食品、电子、制造、消费品到医药的许多技术和工业领域。随着纳米粒子的使用继续激增，评估接触纳米粒子对人类健康的影响至关重要。在众多挑战中，一项主要挑战是了解纳米颗粒表面涂层带来的潜在毒性。为了应对这一挑战，本研究项目旨在揭示纳米颗粒表面不均匀涂层对生物膜结构和功能的影响。纳米颗粒被创造出来，以显示不均匀的表面涂层，类似于在环境中发现的工程纳米颗粒。研究纳米颗粒和生物膜之间的相互作用将为更好地预测工业颗粒的生物影响提供指导。这一知识还将使设计具有受控表面属性的纳米颗粒成为可能，从而实现理想的生物影响。研究人员开展的教育和推广活动将在纳米技术和生物学的界面上普及科学。特别是“纳米生物大使”计划的使用，将把纳米生物科学带给印第安纳州农村社区的学生和普通公众。该项目的总体目标是建立对具有非均质表面化学的纳米颗粒如何影响生物膜结构和功能的定量理解。为了实现这一目标，研究人员建议将重点放在由疏水和带电基团组成的非均质表面，因为这类似于工业纳米粒子在水中的表面化学。我们追求三个具体目标。首先，合成了一系列大小不同、亲水亲油平衡的两亲性纳米颗粒。其次，研究了这种纳米颗粒对支持的脂质双层的完整性和功能的破坏，并确定了其潜在的分子机制。第三，利用巨型脂泡系统阐明了膜性质，包括曲率、组成和脂筏形成对两亲性纳米颗粒与生物膜相互作用的影响。纳米颗粒引起的脂膜变化主要是使用先进的光学和电子显微镜进行量化的。这项研究的发现在纳米颗粒中的不均匀表面化学和它们对生物膜的扰动之间建立了直接的联系。这项研究提供了非常需要但目前还不存在的知识：对非均质表面化学如何影响纳米颗粒和生物膜之间的相互作用的定量理解。

Engineered nanoparticles (particles of inorganic matter with a diameter on the order of tens of nanometers) have made inroads into many technology and industry sectors, from food, electronics, manufacture, consumer products, to medicine. As the use of nanoparticles continues to surge, it is critical to assess how the exposure to nanoparticles impacts human health. One major challenge, among many, is to understand the potential toxicity introduced by the surface coatings on the nanoparticles. To tackle this challenge, this research project is specifically designed to reveal the effect of non-uniform surface coatings of nanoparticles on the structure and function of biomembranes. Nanoparticles are created to display non-uniform surface coatings that resemble engineered nanoparticles found in the environment. Investigations on the interactions between the nanoparticles and the biomembranes will provide guidelines to better predict the biological impact of industrial particles. This knowledge will also enable the design of nanoparticles with controlled surface properties, achieving desirable biological impacts. Educational and outreach activities implemented by the researchers will popularize sciences at the interface of nanotechnology and biology. The use of a "Nano-Bio Ambassadors" program, in particular, will bring nano-bioscience to students in rural communities in Indiana as well as to the general public. The overall objective of this project is to establish a quantitative understanding of how nanoparticles with heterogeneous surface chemistry influence the structure and function of biological membranes. Towards that goal, the researchers propose to focus on heterogeneous surfaces comprised of hydrophobic and charged groups, because this resembles the surface chemistry of industrial nanoparticles in water. Three specific aims are pursued. First, a series of amphiphilic nanoparticles that vary over a range of sizes and in hydrophilic-lipophilic balance are synthesized. Second, the disruption of such nanoparticles to the integrity and function of supported lipid bilayers is investigated and the underlying molecular mechanisms are determined. Third, the effects of membrane properties, including curvature, composition, and lipid raft formation, on interactions between amphiphilic nanoparticles and biomembranes is elucidated using the giant lipid vesicle system. Changes in lipid membranes induced by nanoparticles is mostly quantified using advanced optical and electron microscopies. Findings from this research establishes a direct connection between heterogeneous surface chemistry in nanoparticles and their perturbation to biomembranes. This study provides knowledge that is much needed but currently non-existent: a quantitative understanding of how a heterogeneous surface chemistry impacts interactions between nanoparticles and biomembranes.