Mar 18, 2009

Interaction between C60 variants and lipid bilayer unmasked

Potential applications of the C₆₀ fullerene molecule (the buckyball) to nanomedicine have been widely discussed. Consequently, we need to understand how these molecules interact with cellular components. Of particular importance is how they interact with membranes, which form the outer boundaries of cells. A study recently published in Nanotechnology uses novel computer simulations to explore how chemical derivatization of the surface of a C₆₀ molecule may exert profound effects on its interaction with a lipid bilayer membrane.

Researchers in the Department of Biochemistry, University of Oxford, UK, have used coarse-grained molecular dynamics simulations to determine the relationship between the degree of surface derivatization and the energetic cost for a C₆₀ molecule to enter and cross a lipid bilayer. In coarse-grained simulations each 3 or 4 individual atoms in a molecule are grouped into a single particle, allowing more efficient simulation of longer timescale processes in complex bionano systems.

The experimental literature suggests that certain forms of hydroxylated C₆₀ can cross lipid bilayers and enter cells. In the simulations, seven different C₆₀ variants were explored, ranging from pristine C₆₀, to C₆₀(OH)₂₀ – the latter is a form in which one in every three carbon atoms is modified by hydroxylation.

Varying the degree of derivatization of the surface of C₆₀ led to profound differences in interactions with a lipid bilayer. While pristine C₆₀ partitions into the hydrophobic core of the membrane, C₆₀(OH)₂₀ is unable to enter the membrane and remains in the water surrounding the outside of a cell. Intermediate levels of derivatization, e.g. C₆₀(OH)₁₀, result in a molecule that interacts favourably with the interface between water and membrane, thus promoting entry into cells via bilayer permeation while maintaining water solubility. Such sensitivity of the interaction with membranes to the degree of derivatization of C₆₀ has important implications for potential biomedical applications, such as their targeted drug delivery.

These studies in combination with recent simulations of carbon nanotubes (also published in Nanotechnology) indicate how computer modelling can unmask the interactions of nanomaterials with cellular components. Understanding such interactions is crucial to sustaining advances in nanomedicine.

About the author

Robert D'Rozario, Chze Ling Wee and Jayne Wallace are postdoctoral researchers in the Department of Biochemistry, University of Oxford. Mark Sansom is director of the Structural Bioinformatics and Computational Biochemistry Unit within the department. Research in his group is funded by a number of agencies, including the BBSRC, EPSRC, the James Martin 21st Century School and the Wellcome Trust.