Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes

Recent work has demonstrated that charged gold nanoparticles (AuNPs) protected by an
amphiphilic organic monolayer can spontaneously insert into the core of lipid bilayers to
minimize the exposure of hydrophobic surface area to water. However, the kinetic pathway to
reach the thermodynamically stable transmembrane configuration is unknown. Here, we use
unbiased atomistic simulations to show the pathway by which AuNPs spontaneously insert
into bilayers and confirm the results experimentally on supported lipid bilayers. The critical
step during this process is hydrophobic–hydrophobic contact between the core of the bilayer
and the monolayer of the AuNP that requires the stochastic protrusion of an aliphatic lipid tail
into solution. This last phenomenon is enhanced in the presence of high bilayer curvature and
closely resembles the putative pre-stalk transition state for vesicle fusion. To the best of our
knowledge, this work provides the first demonstration of vesicle fusion-like behaviour in an
amphiphilic nanoparticle system.