How hydrophobic nanoparticles aggregate in the interior of membranes: A computer simulation

Lipid-based dispersion of hydrophobic nanoparticles (NPs) not only gives fundamental insight into how nanomaterials distribute in live cells and organisms, but also provides a quite general route to designing nanocarrier agents in triggered drug delivery and medical imaging. It is not clearly understood how hydrophobic NPs arrange in the interior of a membrane. In this paper, with computer simulation techniques, we demonstrate that hydrophobic NPs having a diameter compared to the hydrophobic thickness of the membrane are capable of clustering in the hydrophobic interior of a cell membrane. Except from the isotropic aggregation, an unexpected linear arrangement of spherical NPs, which is still not found from experiments, is identified here. The free-energy costs associated with linear and isotropic aggregations are computed explicitly to interpret aggregation behavior and the obtained phase diagrams give us a comprehensive understanding of where linear aggregation is expected. In this work we also shows that NP size and membrane tension play key roles in determining the NP aggregate, while the effects of NP concentration and membrane curvature seem to be relatively weak.