Tunable ElectrostaticInteractions of Lipid-CoatedQuantum Dots with Biological Membranes

Abstract Surface functionalization of inorganic quantum dot (QD) nanoparticles is of great interest in the application of these materials toward a wide range of biological applications, where membrane interactions are critical. The use of amphiphilic lipids to functionalize the surfaces of quantum dots represents a promising alternative to produce water-soluble and membrane-active materials with facile tuning of the quantum dot’s surface properties. Here, we demonstrate an experimental approach that yields lipid-coated quantum dots with highly tunable surface charges by controlling the concentration of cationic lipids during preparation. Through fluorescence-activated cell sorting assays, we show that these cationic lipid-coated quantum dots can enhance membrane interactions and increase the membrane labeling density in live HEK293 cells. We further employed coarse-grained molecular dynamics simulations to model the lipid self-assembly process using an implicit solvent force field and subsequently modeled the adsorption of lipid-coated quantum dots to model membranes. Our simulations show that we can control the effective surface charge of lipid-coated quantum dots and influence the strength of adsorption to oppositely charged lipid membranes, a process that is mediated by the release of counterions at the quantum dot-membrane interface. This work supports the future development of biocompatible and water-soluble inorganic nanoparticles with highly tunable surfaces and provides mechanistic insight into how different lipids can influence nanoparticle–membrane interactions at a molecular-scale.