Nanoparticle and Surfactant Interactions with Model Cell Membranes

Abstract

Due to their small size, nanoparticles have the ability to penetrate cell membranes, and are therefore classified as potential human carcinogens. Nanoparticle insertion into targeted cells also proves beneficial for 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 were introduced to a Langmuir phospholipid monolayer, a model of the outer leaflet of the cell membrane. Negatively charged (COO- functionalized) detergent free nanoparticles introduced beneath a zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine monolayer held at constant, physiological pressure solubilized the phospholipid layer, removing material from the air/water interface, to a greater extent than did positively charged (NH3+ functionalized) nanoparticles. To further examine the role of lipid charge, negatively charged 1,2-dilauroyl-sn-glycero-3-phospho-(1′-rac-glycerol) and positively charged 1,2-dimyristoyl-3-trimethylammonium-propane lipid monolayers were used. Nanoparticles of opposite charge removed a larger percentage of the monolayer compared to like-chargedparticle/phospholipid systems illustrating the role of electrostatics.Ionic and non-ionic surfactants, typically present in nanoparticle solutions to prevent aggregation, were introduced beneath the monolayer and all detergents showed significant insertion which directly correlated to surfactant hydrophobicity. Adding a low mol% of surfactant to detergent-free nanoparticle solutions decreased the amount of monolayer destruction compared to nanoparticles alone. At increased detergent concentrations in the nanoparticle solutions, insertion into the monolayers was intermediate in behavior between the particles and surfactant alone. To better understand how nanoparticles and detergents interact with each other and with the membrane, either nanoparticles or detergents were introduced beneath the monolayer, and following a time lapse, the other component was introduced. A model of detergent sequestration by the polystyrene nanoparticles has been developed to explain these results.