Membrane monolayer protrusion mediates a new nanoparticle wrapping pathway

Understanding how nanoparticles (NPs) interact with the lipid membrane is of importance for their potential applications in biomedicine and cytotoxic effects. In this paper, with the aid of computer simulation techniques, we report that NPs can be wrapped by lipid membranes in a pathway different from the conventional endocytic pathway. Our simulation results show that under the conditions of strong NP-membrane adhesion and low membrane tension, NPs can be wrapped by membranes with a pathway regulated by membrane monolayer protrusion. We also find that in the monolayer protrusion mediated wrapping pathway NPs are first trapped in the membrane and the subsequent NP internalization can be achieved by several means, including decreasing the membrane tension, breaking the membrane symmetry between upper and lower leaflets, and exerting an external force on the NPs. The findings from our simulations are well supported by the free energy analysis.