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Understanding how membrane proteins interact with their environment is fundamental to the understanding of their structure, function and interactions. We have performed coarse-grained molecular dynamics simulations on a series of membrane proteins in a membrane environment to examine the perturbations of the lipids by the presence of protein. We analyze these perturbations in terms of elastic membrane deformations and local lipid protein interactions. However these two factors are insufficient to describe the variety of effects that we observe and the changes caused by membranes proteins to the structure and dynamics of their lipid environment. Other factors that change the conformation available to lipid molecules are evident and are able to modify lipid structure far from the protein surface, and thus mediate long-range interactions between membrane proteins. We suggest that these multiple modifications to lipid behavior are responsible, at the molecular level, for the lipophobic effect we have proposed to account for our observations of membrane protein organization.

Despite the major interest in membrane proteins at functional, genomic, and therapeutic levels, their biochemical and structural study remains challenging, as they require, among other things, solubilization in detergent micelles. The complexity of this task derives from the dependence of membrane protein structure on their anisotropic environment, influenced by a delicate balance between many different physicochemical properties. To study such properties in a small protein-detergent complex, we used fluorescence measurements and molecular dynamics (MD) simulations on the transmembrane part of glycophorin A (GpAtm) solubilized in micelles of dihexanoylphosphatidylcholine (DHPC) detergent. Fluorescence measurements show that DHPC has limited ability to solubilize the peptide, while MD provides a possible molecular explanation for this. We observe that the detergent molecules are balanced between two different types of interactions: cohesive interactions between detergent molecules that hold the micelle together, and adhesive interactions with the peptide. While the cohesive interactions are detergent mediated, the adhesion to the peptide depends on the specific interactions between the hydrophobic parts of the detergent and the topography of the peptide dictated by the amino acids. The balance between these two parameters results in a certain frustration of the system and rather slow equilibration. These observations suggest how molecular properties of detergents could influence membrane protein stabilization and solubilization.

and that the lipids within are well ordered. This research characterizes the lipid packing and phase behavior of such domains in bilayers composed of sphingomyelin, ceramide, DPPC, POPC and cholesterol. Over the past 30 years, X-ray studies were performed on either lipid monolayers, or multilayers. Several attempts have been made over the past 20 years, to perform experiments on single lipid bilayers, all of which have failed due to the strong scattering of the bilayer's surrounding water. In order to overcome this challenge we have developed a new system, which enables measurements of single hydrated lipid bilayers using synchrotron radiation. 1 This research provided, for the first time, knowledge on the interactions between the opposing lipids of each leaflet at the core of the bilayer. Comparisons with lipid monolayers made of the same lipid composition showed that the phase behavior of the ordered domains differs greatly, indicating strong correlation between the opposing leaflets of the bilayer. 2 Large quantities of cholesterol monohydrate crystals are found in atherosclerotic plaques. Studies have shown that these crystals are an early cause of inflammation. We managed to characterize the conditions under which cholesterol molecules nucleate at the lipid bilayer. Results demonstrate that cholesterol nucleation depends on the lipid composition. 2,3 The study was awarded the 2011 Barenholz Prize for basic research on sphingolipids.

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