Understanding and exploiting lipid-lipid interactions

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Our efforts are primarily devoted to the structural characterization of lipid self-assemblies in order to gain a better understanding of the structure-function relationships for lipids in biological systems. First, we are interested in a family of proteins found in the seminal plasma, which extract selectively, by an unknown mechanism, phosphatidylcholine and cholesterol from sperm membranes, a critical step in the sperm maturation. We propose that the lipid sorting is based on the local curvature of the lipid membranes. To examine this hypothesis, we will probe the membrane curvature at the molecular level, using solid-state 2H NMR. We will also use confocal fluorescence microscopy (with fluorescent labelled lipids) to determine at the microscopic level, the lipid distribution in the self-assemblies resulting from the interactions with these proteins. Finally we will determine quantitatively the lipid specificity by the analysis of the particles resulting from the lipid extractions by these proteins. Second, the lipids of the top layer of the epidermis are largely responsible for the skin impermeability, a vital property linked to the significant proportion of lipid in crystalline phase. We will examine the structure and the dynamics of the formation of this solid phase in order to gain a better understanding of the origin of skin impermeability. By using an infrared microscope equipped with a focal plane array, it will be possible characterize the formation of the crystalline phases (induced by temperature changes or enzymatic activity) in parallel with the formation of domains with heterogeneous lipid compositions at the microscopic scale. The role of different molecular components of the stratum corneum will be examined. Third, we recently discovered the possibility to form non-phospholipid liposomes (NPL) using monoacylated amphiphiles and sterols. These NPL have a very high cholesterol content, they display a remarkable impermeability and an interesting sensitivity to pH. We want to develop a detailed understanding of the molecular structure of these novel liposomes and to create an extended family of these NPL for which the release of the entrapped material can be triggered by various stimuli, including pH, temperature, and light.