Size-dependent aggregation of hydrophobic nanoparticles in lipid membranes

The aggregation of nanoparticles affects their reactivity, transport across biological membranes, uptake into cells, toxicity, and fate in the environment. In the case of membrane-embedded, hydrophobic nanoparticles the relationship between size and aggregation pattern is not well understood. Here, we explore this relationship for the case of spherically symmetrical nanoparticles using the MARTINI coarse-grained force field. We find that the free energy of dimerization depends strongly on nanoparticle size: the smallest molecules (mimicking C60 fullerene) aggregate only weakly, the largest ones form large three-dimensional aggregates causing major deformations in the host membrane, and the intermediate-sized particles show a tendency to form linear aggregates. Suppressing membrane undulations reduces very significantly aggregation, and substantially abolishes linear aggregation, suggesting a relationship between membrane curvature and aggregation geometry. At low concentration, when placed on membranes of variable curvature, the intermediate size nanoparticles move rapidly to high curvature regions - suggesting that they can sense membrane curvature. At high concentration, the same nanoparticles induce massive membrane deformations, without affecting the mechanical stability of the membrane - suggesting that they can generate membrane curvature.