Surfactants, Salt, and pH Alter Nanoparticle-Model Cell Membrane Interactions

Abstract

Due to their small size, nanoparticles have the ability to penetrate pulmonary and vascular tissue, and as a result, are classified as potential human carcinogens. On the other hand, nanoparticle insertion into targeted cells can play a key role in drug delivery and gene therapy applications, prompting a need to more thoroughly characterize nanoparticle/membrane interactions. Polystyrene nanoparticles with modifications in surface functionalization and detergent conditions remain monodisperse in a variety of aqueous solutions as measured by dynamic light scattering, but tend to aggregate in phosphate buffered saline at neutral pH potentially due to electrostatic screening effects. Calcein leakage assays with small unilamellar egg phosphatidylcholine vesicles were run to measure their interactions with nanoparticles and determine applicability of previous experiments performed with lipid monolayers at the air-water interface that modeled the outer leaflet of a cell membrane. In pure water, adding surfactant to detergent-free nanoparticle solutions increased the magnitude of membrane permeabilization compared to nanoparticles alone. In a buffered solution, the opposite was true; addition of surfactant decreased the nanoparticle induced membrane permeabilization. To better understand nanoparticle-detergent-membrane interactions, either nanoparticles or detergents were individually introduced to the vesicles, and following a time lapse, the other component was introduced. A model of detergent sequestration by the polystyrene nanoparticles explains these results and provides insight to the mechanism of vesicle leakage caused by surfactant-nanoparticle mixtures.