Membrane-embedded nanoparticles can modulate lipid membrane permeability

Lipid bilayers possess a characteristic hydrophobic interior that indiscriminately blocks passive transport of polar molecules across biological membranes. Membrane proteins controllably modify this barrier property by enabling selective transport in response to environmental stimuli. We have previously demonstrated that gold nanoparticles functionalized with a monolayer of amphiphilic ligands can non-disruptively insert into lipid membranes and induce perturbations of functional significance. In this work, we use molecular dynamics simulations to investigate how the properties of these membrane-bound particles can be exploited for altering the permeability of small molecules across lipid membranes in a manner that is analogous to the behavior of membrane proteins. We perform free energy calculations to systematically investigate how membrane permeability is modified by morphology, surface chemistry, and embedding state of the nanoparticle. Using unbiased simulations, we also suggest possible strategies for utilizing these nanoparticles as biomimetic membrane channels that are responsive to external stimuli such as membrane tension and ionic imbalance.