Entrapment and Voltage-Driven Reorganization of Hydrophobic Nanoparticles in Planar Phospholipid Bilayers.

Abstract

Engineered nanoparticles (NPs) possess diverse physical and chemical properties, which make them attractive agents for targeted cellular interactions within the human body. Once affiliated with the plasma membrane, NPs can become embedded within its hydrophobic core, which can limit the intended therapeutic functionality and affect the associated toxicity. As such, understanding the physical effects of embedded NPs on a plasma membrane is critical to understanding their design and clinical use. Here, we demonstrate that functionalized, hydrophobic gold NPs dissolved in oil can be directly trapped within the hydrophobic interior of a phospholipid membrane assembled using the droplet interface bilayer technique. This approach to model membrane formation preserves lateral lipid diffusion found in cell membranes and permits simultaneous imaging and electrophysiology to study the effects of embedded NPs on the electromechanical properties of the bilayer. We show that trapped NPs enhance ion conductance and lateral membrane tension in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) bilayers while lowering the adhesive energy of the joined droplets. Embedded NPs also cause changes in bilayer capacitance and area in response to applied voltage, which are nonmonotonic for DOPC bilayers. This electrophysical characterization can reveal NP entrapment without relying on changes in membrane thickness. By evaluating the energetic components of membrane tension under an applied potential, we demonstrate that these nonmonotonic, voltage-dependent responses are caused by reversible clustering of NPs within the unsaturated DOPC membrane core; aggregates form spontaneously at low voltages and are dispersed by higher transmembrane potentials of magnitude similar to those found in the cellular environment. These findings allow for a better understanding of lipid-dependent NP interactions, while providing a platform to study relationships between other hydrophobic nanomaterials and organic membranes.