Aqueous solutions next to phospholipid membrane surfaces: insights from simulations.

It is well established that water plays a very important role in the functioning of biological molecules and their assemblies. Among such molecular assemblies are biological membranes. The self-assembly of these membranes is driven by the hydrophobic effectsa clear consequence of their aqueous environment. Water contributes to the mechanism responsible for membrane/membrane interaction and contributes to the assisted passage of ions and other molecules across biomembranes through special membrane-embedded proteins. Since natural biomembranes represent complicated assemblies of molecules, their study is extremely involved. To simplify the task, the properties of biomembranes are often probed using model membranes containing one type of phospholipid molecule or a simple mixture of lipid molecules. Different experimental techniques are used to study properties of model membranes and their hydration water. The structural properties of membranes and the positions of lipid fragments and hydration water can be measured with the help of X-ray and neutron scattering techniques.1,2 Neutron scattering has also proved to be very useful in the study of the interaction between biomembranes and their hydration water.3 NMR spectroscopy emerged as one of the most important tools used for the study of a large variety of issues related to changes in the structural and dynamical properties of membranes due to membrane hydration. Examples of issues probed by NMR include headgroup conformational changes as a function of the water hydration level,4 permeation of water across the membrane,5 and dynamical properties such as water residence times.6 Infrared spectroscopy7 can provide information on the hydrogen bonding between water and biomolecules, and fluorescence spectroscopy can probe the dynamics of water molecules in the hydration shell.8 To study interactions between membranes and how properties of water in the interbilayer spaces influence these interactions, osmotic stress9 and humiditycontrolled osmotic stress techniques are used.10 The thermodynamics of hydration are studied using new calorimetric methods that allow for separate determination of the energetic and entropic contributions to the dehydration process.11 A more detailed overview of these techniques is provided in a recent excellent review on the water/phospholipid model membrane interactions written by Milhaud.12 In addition to the above-mentioned experimental techniques, computer simulation techniques that employ molecular dynamics and/or Monte Carlo methods are also applied toward the study of structural and dynamical properties of model membranes and their hydration water.13-23 The first full molecular detail simulation done on a system consisting of a bilayer containing a mixture of ternary alcohol with fatty acid and its solvating water was performed by Egberts and Berendsen in 1988.24 Full molecular detailed simulations of phospholipid bilayers solvated in water were performed in the early nineties (see ref 13 for a detailed review of this earlier work). At the present time, there exists a vast amount of literature that deals with computer simulation studies of biomembranes, and it is probably not even possible to summarize all the work described in this literature in one review. Therefore, we will limit our discussion to the subject of computer simulation studies of the aqueous-solution/ model-biomembrane interface since this aspect of the recent * To whom correspondence should be addressed. E-mail: [email protected]. Telephone: 919-962-1218. Fax: 919-962-2388. † Current location: The Scripps Research Institute. ‡ Current location: The Illinois Institute of Technology. 1527 Chem. Rev. 2006, 106, 1527−1539