Interaction of amphiphilic nanoparticles with structurally perturbed lipid membranes

Abstract

Understanding the interactions between nanoparticles and lipid membranes is important for applications such as drug delivery and membrane-protein mimetics. Perturbations such as area asymmetry and lateral tension affect these interactions by inducing various structural changes to the membranes. We use molecular dynamics simulations to demonstrate that the introduction of area asymmetry to a bilayer membrane significantly decreases the insertion latency of amphiphilic gold nanoparticles into both the densely and sparsely packed leaflets. We further demonstrate using transition state analysis that the dominant mechanisms for insertion into the dense and sparse leaflets are lipid desorption and lipid tail protrusions, respectively. These findings are supported by potential of mean force calculations showing that the energy barrier to protrusion is lower in the sparse leaflet, while that of desorption is lower in the dense leaflet. We also demonstrate that the structural characteristics of the bilayer when subject to lateral tension are similar to that observed in membranes with area asymmetry, suggesting a similar reduction in insertion latency. Further, we observe that lateral tension also increases the likelihood of nanoparticle ligands flipping across the bilayer, which is necessary for the nanoparticle adopting a stable symmetric configuration in the membrane.