Correlating Nanoparticle-Induced Biomembrane Perturbation with Heterogeneous Surface Chemistry

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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.