The composition of the plasma membrane of malignant cells is thought to influence the cellular uptake of cisplatin and to take part in developing resistance to this widespread anti-cancer drug. In this work we study the permeation of cisplatin through the model membranes of normal and cancer cells using molecular dynamics simulations. A special attention is paid to lipid asymmetry and cholesterol content of the membranes. The loss of lipid asymmetry, which is common for cancer cells, leads to a decrease in their permeability to cisplatin by one order of magnitude in comparison to the membranes of normal cells. The change in the cholesterol molar ratio from 0% to 33% also decreases the permeability of the membrane by approximately one order of magnitude. The permeability of pure DOPC membrane is 5–6 orders of magnitude higher than one of the membranes with realistic lipid composition, which makes it as an inadequate model for the studies of drug permeability.

In this work we conduct a systematic analysis of the influence of curvature on various properties of a realistic model of mammalian plasma membrane with asymmetric lipid content of monolayers and a realistic concentration of cholesterol. In order to do this we developed new technique for simulating membranes with the global membrane curvature restricted to any desirable value while keeping free lateral diffusion of the lipids and without introducing artifacts or perturbing the membrane structure. We show that the thickness of the hydrophobic core of the concave monolayer decreases by approximately 1.3 Å in comparison to that of the flat membrane, while the thickness of the convex monolayer does not change. The order parameter of the lipid tails decreases significantly in the certain layers of the curved membrane. The area per lipid increases in the convex monolayer and decreases in the concave monolayer. The cholesterol inclination angle decreases when the curvature of a particular monolayer changes from concave to convex. The amount of cholesterol in the minor fraction located between the membrane leaflets is zero in the membrane with positive curvature and increases to 1.7% in the flat membrane and to 2.5% in the membrane with negative curvature.

The adsorption of small molecules $({\mathrm{N}}_2,$ ${\mathrm{O}}_2,$ CO, ${\mathrm{CO}}_2,$ ${\mathrm{H}}_2\mathrm{O},$ and HF) in model ropes of carbon nanotubes has been studied to determine the main parameters (stable adsorption sites, potential barriers, $\dots )$ which define the ability of carbon nanotubes to select small molecules through their different behavior in the diffusion mechanism. When the polarization of the nanotubes is taken into account in the semiempirical potentials, it has a significant influence on the adsorption of polar species. Examination of the potential maps along the ropes shows that the nature and the stability of the adsorption sites are strongly dependent on the molecular species and on the diameter of the tubes. For a small rope formed with (10,10) single-wall nanotubes, different trapping sites are favored by the molecules considered. Furthermore the corresponding trapping well depths are sufficiently selective to discriminate the species. Improving the size homogeneity of the ropes and judiciously calibrating their diameter would provide an efficient mean of selecting molecular species.

Carbon nanotubes have been proposed to be efficient nanovectors able to deliver genetic or therapeutic cargo into living cells. However, a direct evidence of the molecular mechanism of their translocation across cell membranes is still needed. Here, we report on an extensive computational study of short (5 nm length) pristine and functionalized single-walled carbon nanotubes uptake by phospholipid bilayer models using all-atom molecular dynamics simulations. Our data support the hypothesis of a direct translocation of the nanotubes through the phospholipid membrane. We find that insertion of neat nanotubes within the bilayer is a “nanoneedle” like process, which can often be divided in three consecutive steps: landing and floating, penetration of the lipid headgroup area and finally sliding into the membrane core. The presence of functional groups at moderate concentrations does not modify the overall scheme of diffusion mechanism, provided that their deprotonated state favors translocation through the lipid bilayer.

Study of the mechanisms understanding how chemically functionalized carbon nanotubes internalize into mammalian cells is important in view of their design as new tools for therapeutic and diagnostic applications. The initial contact between the nanotube and the cell membrane allows elucidation of the types of interaction that are occurring and the contribution from the types of functional groups at the nanotube surface. Here we offer a combination of experimental and theoretical evidence of the initial phases of interaction between functionalized carbon nanotubes with model and cellular membranes. Both experimental and theoretical data reveal the critical parameters to determine direct translocation of the nanotubes through the membrane into the cytoplasm as a result of three distinct processes that can be summarized as landing, piercing and uptake.