Correlating Nanoparticle-Induced Biomembrane Perturbation with Heterogeneous Surface Chemistry

工程纳米粒子（直径约为数十纳米的无机物颗粒）已经进入许多技术和工业领域，从食品，电子，制造，消费品到医药。随着纳米粒子的使用持续激增，评估纳米粒子暴露如何影响人类健康至关重要。其中一个主要挑战是了解纳米颗粒表面涂层引入的潜在毒性。为了应对这一挑战，该研究项目专门设计用于揭示纳米颗粒的非均匀表面涂层对生物膜结构和功能的影响。 纳米颗粒被创建为显示不均匀的表面涂层，类似于环境中发现的工程纳米颗粒。研究纳米颗粒与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。这一知识也将使纳米粒子的设计与控制的表面特性，实现理想的生物影响。研究人员开展的教育和外联活动将普及纳米技术和生物学之间的科学。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以及公众。这个项目的总体目标是建立一个定量的了解如何与异质表面化学纳米粒子影响生物膜的结构和功能。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异质表面上，因为这类似于水中工业纳米颗粒的表面化学。有三个具体目标。首先，合成了一系列在一定尺寸范围内变化并且具有亲油-亲油平衡的两亲性纳米颗粒。其次，这种纳米粒子的完整性和功能的支持脂质双层的破坏进行了研究，并确定了潜在的分子机制。第三，膜的性质，包括曲率，组合物，和脂筏的形成，两亲性纳米粒子和生物膜之间的相互作用的影响，阐明了使用巨脂囊泡系统。纳米颗粒引起的脂质膜的变化主要是使用先进的光学和电子显微镜进行定量。这项研究的发现建立了纳米颗粒的异质表面化学与其对生物膜的扰动之间的直接联系。这项研究提供了非常需要但目前不存在的知识：定量了解异质表面化学如何影响纳米颗粒和生物膜之间的相互作用。

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.