Identification of possible sources of nanotoxicity from carbon nanotubes inserted into membrane bilayers using membrane interaction quantitative structure-activity relationship analysis

Four possible sources of cellular toxicity due to the insertion of a carbon nanotube into a dimyristoylphosphatidylcholine (DMPC) membrane bilayer were explored using the membrane interaction quantitative structure-activity relationship methodology. Comparisons of (i) the structural organization of the membrane bilayer, (ii) dynamical features of the membrane bilayer, and (iii) transport of small polar molecules across the membrane bilayer were carried out with, and without; a carbon nanotube inserted into the bilayer. A fourth study was performed to determine how the transport of solvated ions through the inserted nanotube might alter the structure of the membrane bilayer. Two large changes in the bilayer occur due to insertion of the carbon nanotube. First, there is an alteration in the packing of the DMPC bilayer molecules, which extends at least 18 angstrom from the nanotube, and includes the creation of a relatively open, unoccupied cylindrical ring of 2-4 angstrom thickness directly around the nanotube. Second, the same bilayer structure, which undergoes the change in structural organization, also becomes much more rigid than when the nanotube is not inserted. Solvated calcium ions are predicted to preferentially transport through the inserted nanotube as compared to hydrated sodium ions, but the solvated calcium ion also produces an alteration in the local bilayer structure as it passes through the nanotube. The total diffusion coefficient of ethanol through the membrane bilayer increases by about 35% in the presence of the inserted nanotube. Urea and caffeine also undergo increases in their diffusion coefficients for transport through the bilayer, due to the inserted nanotube, but these increases are less than that of ethanol. Each of the three penetrants also diffuses more directly through the membrane bilayer in the presence of the nanotube, especially caffeine and urea.