Response to Comment by Almeida et al.: Free Area Theories for Lipid Bilayers -- Predictive or Not?

¹ Laboratory of Physics and Helsinki Institute of Physics, Helsinki University of Technology
² Laboratory of Computational Engineering, Helsinki University of Technology
³ Wihuri Research Institute

^* To whom correspondence should be addressed. E-mail: ilp{at}fyslab.hut.fi.

Submitted on May 23, 2005
Revised on May 23, 2005
Accepted on 24 May 2005

	Abstract

Free area theories for lateral diffusion in lipid bilayers are reviewed and discussed. It has been suggested by Almeida et al. that free area theories yield quantitative predictions for lateral diffusion coefficients of lipids. We investigate the plausibility of this suggestion by first sketching what is to be expected of a quantitative theory with predictive power, and subsequently examining whether existing free area theories comply to these expectations. Our conclusion is that current free area theories for lipid bilayers are not quantitative theories with predictive power. They involve a number of adjustable parameters, all of which are not estimated independently, but derived from fitting the theory to the very data whose behavior the theory is supposed to predict. Further, the interpretation and behavior of some of the parameters are ambiguous. The best example is the so-called activation barrier, whose qualitative behavior with the cholesterol concentration in a DMPC bilayer varies depending on the experimental method used to generate the input data and the exact assumptions made to formulate the theory. Independent determination of the activation barrier from numerical simulations or experiments appears to be very difficult.

Key Words: diffusion, free area, free volume, lipid bilayer, lipid membrane, molecular dynamics

This article has been cited by other articles:

				T. Rog, M. Pasenkiewicz-Gierula, I. Vattulainen, and M. Karttunen What Happens if Cholesterol Is Made Smoother:: Importance of Methyl Substituents in Cholesterol Ring Structure on Phosphatidylcholine-Sterol Interaction Biophys. J., May 15, 2007; 92(10): 3346 - 3357. [Abstract] [Full Text] [PDF]

				K. J. Seu, L. R. Cambrea, R. M. Everly, and J. S. Hovis Influence of Lipid Chemistry on Membrane Fluidity: Tail and Headgroup Interactions Biophys. J., November 15, 2006; 91(10): 3727 - 3735. [Abstract] [Full Text] [PDF]

				E. Falck, J. T. Hautala, M. Karttunen, P. K. J. Kinnunen, M. Patra, H. Saaren-Seppala, I. Vattulainen, S. K. Wiedmer, and J. M. Holopainen Interaction of Fusidic Acid with Lipid Membranes: Implications to the Mechanism of Antibiotic Activity Biophys. J., September 1, 2006; 91(5): 1787 - 1799. [Abstract] [Full Text] [PDF]

				J. P. Kampf, D. Cupp, and A. M. Kleinfeld Different Mechanisms of Free Fatty Acid Flip-Flop and Dissociation Revealed by Temperature and Molecular Species Dependence of Transport across Lipid Vesicles J. Biol. Chem., July 28, 2006; 281(30): 21566 - 21574. [Abstract] [Full Text] [PDF]