Recent toxicology studies suggest that nanosized aggregates of fullerene molecules can enter cells and alter their functions, and also cross the blood-brain barrier. However, the mechanisms by which fullerenes penetrate and disrupt cell membranes are still poorly understood. Here we use computer simulations to explore the translocation of fullerene clusters through a model lipid membrane and the effect of high fullerene concentrations on membrane properties. The fullerene molecules rapidly aggregate in water but disaggregate after entering the membrane interior. The permeation of a solid-like fullerene aggregate into the lipid bilayer is thermodynamically favoured and occurs on the microsecond timescale. High concentrations of fullerene induce changes in the structural and elastic properties of the lipid bilayer, but these are not large enough to mechanically damage the membrane. Our results suggest that mechanical damage is an unlikely mechanism for membrane disruption and fullerene toxicity.

Lipid peroxidation plays an important role in cell membrane damage. We investigated the effect of lipid peroxidation on the properties of 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) lipid bilayers using molecular dynamics simulations. We focused on four main oxidation products of linoleic acid with either a hydroperoxide or an aldehyde group: 9-trans, cis-hydroperoxide linoleic acid, 13-trans, cis-hydroperoxide linoleic acid, 9-oxo-nonanoic acid, and 12-oxo-9-dodecenoic acid. These oxidized chains replaced the sn-2 linoleate chain. The properties of PLPC lipid bilayers were characterized as a function of the concentration of oxidized lipids, with concentrations from 2.8% to 50% for each oxidation product. The introduction of oxidized functional groups in the lipid tail leads to an important conformational change in the lipids: the oxidized tails bend toward the water phase and the oxygen atoms form hydrogen bonds with water and the polar lipid headgroup. This conformational change leads to an increase in the average area per lipid and, correspondingly, to a decrease of the bilayer thickness and the deuterium order parameters for the lipid tails, especially evident at high concentrations of oxidized lipid. Water defects are observed in the bilayers more frequently as the concentration of the oxidized lipids is increased. The changes in the structural properties of the bilayer and the water permeability are associated with the tendency of the oxidized lipid tails to bend toward the water interface. Our results suggest that one mechanism of cell membrane damage is the increase in membrane permeability due to the presence of oxidized lipids.