Polyunsaturation in Lipid Membranes: Dynamic Properties and Lateral Pressure Profiles Samuli Ollila, ²,‡ Marja T. Hyvo 1 nen, ²,§ and Ilpo Vattulainen* ,²,‡, | Laboratory of Physics and Helsinki Institute of Physics, Helsinki UniVersity of Technology, P.O. Box 1100, FI-02015 HUT, Finland, Institute of Physics, Tampere UniVersity of Technology, P.O. Box 692, FI-33101 Tampere, Finland, Wihuri Research Institute, Kalliolinnantie 4, FI-00140 Helsinki, Finland, and Memphyss Center for Biomembrane Physics, Physics Department, UniVersity of Southern Denmark, CampusVej 55, DK-5230 Odense M, Denmark ReceiVed: August 22, 2006; In Final Form: December 22, 2006 We elucidate the influence of unsaturation on single-component membrane properties, focusing on their dynamical aspects and lateral pressure profiles across the membrane. To this end, we employ atomistic molecular dynamics simulations to study five different membrane systems with varying degrees of unsaturation, starting from saturated membranes and systematically increasing the level of unsaturation, ending up with a bilayer of phospholipids containing the docosahexaenoic acid. For an increasing level of unsaturation, we find considerable effects on dynamical properties, such as accelerated dynamics of the phosphocholine head groups and glycerol backbones and speeded up rotational dynamics of the lipid molecules. The lateral pressure profile is found to be altered by the degree of unsaturation. For an increasing number of double bonds, the peak in the middle of the bilayer decreases. This is compensated for by changes in the membrane-water interface region in terms of increasing peak heights of the lateral pressure profile. Implications of the findings are briefly discussed. I. Introduction The level of unsaturation is a strictly regulated property of all biological membranes, including cell membranes as well as intracellular specialized membranes. Unsaturated lipids are known to play a significant role in membranes, the topical and highly prominent example being the importance of polyunsatu- rated lipids such as those containing docosahexaenoic acid (DHA); see refs 1-4 and references therein. The lipids containing DHA have been suggested, for example, to modulate the membrane elastic stress and thereby influence the function- ality of integral membrane proteins. 5 Long-chain ω-3-polyun- saturated fatty acids are also known to induce various health benefits in terms of preventing cancer and heart diseases, among others. 6 Nowadays, double bonds are known to affect various structural membrane properties such as the area per lipid and the ordering of the acyl chains. 3,7 Yet it is evident that the ideas of the role of double bonds have changed over time as more data and more qualified methodology has become available. For instance, originally double bonds were considered as rigidifying structures in membranes due to the natural rigidity of a cis type double bond, 8,9 whereas recent studies have revealed unsaturated hydrocarbon chains to be remarkably flexible due to extra- ordinary isomerization of the single bonds neighboring the double bonds. 4,7,10,11 This recent progress also highlights the fact that, in contrast to the structural properties of unsaturated membranes, much less attention has been paid to understand the influence of double bonds on the dynamic properties of lipids. These effects are discussed in more detail in this article. An especially interesting and poorly understood property of lipid membranes is the distribution of local pressure inside a bilayer, the so-called lateral pressure profile. The lateral pressure profile is related to many important macroscopic and measurable quantities, such as surface tension, surface free energy, and spontaneous curvature. 12 Furthermore, Cantor has rather recently proposed an interesting idea that changes in the lateral pressure profile may affect the functionality of mechanosensitive proteins in cell membranes, 13 which could explain, for example, the action of general anesthetics 14,15 and the coupling between protein functionality and lipid content. 14,16 It is noteworthy that Cantor’s mean-field calculations 14 and atomic-scale molecular dynamics simulations of Carrillo-Tripp and Feller 17 have suggested that double bonds shift repulsive pressure from the middle of the membrane toward the interfacial region. This change has been suggested to lead to the observed increase in rhodopsin activity due to polyunsaturated lipids. 14 Interestingly, the same idea concerning the dependence of rhodopsin activity on unsaturation level has been presented earlier by Brown et al. 18-20 who discussed the role of curvature stress, which in turn is related to the lateral pressure profile and the elasticity of a membrane. Despite the rather substantial number of studies on unsaturated membranes, it is evident that not even the recent findings do fully explain the functional properties of double bonds in membranes. Of particular interest would be to clarify the interplay between double bonds, lateral pressure, and the dynamics of membranes for varying degrees of unsaturation. That would also render the understanding of protein functionality in unsaturated membranes more comprehensible. In this work, we present a thorough systematic analysis of unsaturated lipid membranes studied through atomic-scale molecular dynamics simulations, focusing on the dynamics and the lateral pressure profiles. Starting from saturated lipids, we systematically increase the level of unsaturation and end up with * Author to whom correspondence should be addressed. E-mail: Ilpo.Vattulainen@csc.fi. ² Helsinki University of Technology. ‡ Tampere University of Technology. § Wihuri Research Institute. | University of Southern Denmark. 3139 J. Phys. Chem. B 2007, 111, 3139-3150 10.1021/jp065424f CCC: $37.00 © 2007 American Chemical Society Published on Web 03/03/2007