Lipid Diffusion, Free Area, and Molecular Dynamics Simulations

Abstract

In a recent article in Biophysical Journal, Falck et al. (2004) present a molecular dynamics (MD) study of phosphatidylcholine (PC)/cholesterol (Chol) bilayers, focusing on the lipid packing and its relation to free area and lateral diffusion of lipids. A significant comparison is made between their MD results and our experimental diffusion measurements using fluorescence recovery after photobleaching (FRAP) and the analysis of those experiments using the free area model (Almeida et al., 1992). In contrast to our conclusion, Falck et al. state that the free area model does not quantitatively represent lipid diffusion. Furthermore, their simulations predict a much stronger effect of cholesterol on diffusion than found experimentally. In our opinion, as written, some of the statements of Falck et al. are prone to misinterpretation. The criticism of the free are model based on the MD simulations is flawed because comparison is made between different systems. If the proper systems are compared, the free area model actually predicts the correct result for lipid diffusion, whereas the MD simulations do not. In this Comment to the Editor, we present our views on the problem and clarify several of the issues. Finally, we attempt to resolve the apparent quantitative disagreement between the MD simulations and our experiments on lipid diffusion.