(197b) Simulations of the Bilayer-Mediated Assembly of Cationic Nanoparticles on Phase-Separated Lipid Bilayers

Authors: 
Sheavly, J. K., University of Wisconsin-Madison
Van Lehn, R. C., University of Wisconsin-Madison
Understanding interactions between functionalized gold nanoparticles (NPs) and lipid bilayers is essential for their use in biomedical applications. Experiments and continuum-scale simulations have suggested that small (~5 nm diameter) cationic NPs aggregate when adsorbed to the surface of zwitterionic lipid bilayers despite being stable in aqueous solution, suggesting that bilayer-mediated interactions facilitate assembly. Determining the origin of these effects and the impact of other bilayer features, such as lipid phase separation, on the interfacial assembly of NPs would enable the design of NPs for applications that require NP assembly, such as photothermal therapy.

In this work, we use chemically specific coarse-grained molecular dynamics simulations to show that cationic NP adsorption to lipid bilayers is driven by a balance between favorable NP-lipid interactions and the unfavorable mechanical deformation of the bilayer to create local curvature. The minimization of induced curvature near topological features, such as boundaries between stiff and flexible phase-separated bilayer domains, enhances NP adsorption. Since these driving forces do not depend on solvent-mediated interactions, we next parameterize an implicit solvent model to model larger length-scale phenomena involving multiple adsorbed NPs. We measure the bilayer-mediated interactions between two adsorbed NPs by comparing the aggregation free energy on a bilayer to that in solution. These simulations indicate that the bilayer contributes an attractive interaction between the nanoparticles associated with the reduction in induced curvature. We further show that that the association of 3 NPs is less favorable than the aggregation of 2 NPs and leads to linear aggregates. Finally, we find that NPs align along phase boundaries and prefer dimerization as opposed to larger structures. These simulation results indicate that bilayer curvature mediates interactions between adsorbed NPs and favors alignment near phase boundaries. Future investigation will include the influence of size, shape, and surface chemistry on the self-assembly of adsorbed NPs.