LAUSR

Understanding the interactions between nanoparticles (NP) and lipid bilayers (LB), which constitute the foundations of cell membranes, is important for emerging biomedical technologies, as well as for assessing health threats related to nanoparticle commercialization. Applying dissipative particle dynamic simulations, we explore adhesion, intake, and release of hydrophobic nanoparticles by DMPC bilayers. To replicate experimental conditions, we develop a novel simulation setup for modeling membranes at isotension conditions. NP-LB interactions are quantified by the free energy landscape calculated by the ghost tweezers method. NPs are studied z of diameter 2 nm (comparable with the LB hydrophobic core), 4 nm (comparable with the LB thickness) and 8 nm (exceeding the LB thickness). NPs are pre-covered by an adsorbed lipid monolayer. It is shown that NP translocation across LB includes (1) NP intake into the hydrophobic core via merging of the monolayer adsorbed on NP with the outer leaflet of bilayer (2) NP release via formation and rupture of a lipid junction connecting NP and LB. Both stages are associated with free energy barriers. The barrier for the intake stage increases with the NP size and becomes prohibitively high for 8 nm NP. The barriers for the release stage are significantly higher which implies that the release stage controls the translocation rate and dynamics. The release energy barrier of 4 nm NP is found smaller than those for 2 and 8 nm NPs which implies the existence of the optimal NP size for unforced trans-membrane transport. Based on the calculated free energy landscape, the dynamics of unforced transport of NP across LB is evaluated using the Fokker-Planck equation, which mimics NP diffusion along the free energy landscape with multiple attempts to reach the barrier. We found that the number of attempts required for successful translocation scales exponentially with the energy barrier.