Understanding and exploiting lipid interactions

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Our research program aims at characterizing the structure and the dynamics of biological materials involving lipids to understand the mechanism of key biological events, and to develop novel biomimetics. * Some peptides and some proteins can induce lipid efflux from membranes; this phenomenon plays central roles in biological processes such as sperm maturation, and reverse transport of cholesterol. Despite the prime importance of these lipid effluxes, their mechanisms are not understood at the molecular level. We will characterize detergent-, peptide- or protein-induced lipid extraction from model membranes to define the key interactions dictating the extraction of specific lipids from membranes in order to better understand these processes.* The lipids of the stratum corneum (SC), the top layer of the epidermis, are largely responsible for the skin impermeability. This exceptional barrier is linked to the unusual crystalline phase formed by a significant proportion of its lipids. Recently, we discovered that this matrix may include hydrocarbon nanodrops, an hypothesis that may lead to reconsider our understanding of the structure/function of SC. We will continue to examine the structure and the dynamics of SC models to identify the molecular parameters required for the formation of this unique solid/liquid matrix and to assess the role of the solid/liquid balance in skin impermeability. The resulting understanding of SC lipid self-assembly will contribute to maintaining a healthy skin barrier, and potentially to altering the barrier for transdermal drug delivery.* My group is developing a novel platform of liposomes formed with a monoalkylated amphiphile and a sterol, and displaying distinct properties including a very low permeability and a very good stability in harsh milieus. In the next granting period, we propose i) to characterize key bilayer processes, such as lipid flip-flop, and cholesterol oxidation; these findings will contribute to design improved nanocarriers and may provide novel concepts in understanding some biological processes b) to examine the possibility of making non phospholipid liposomes using sugar-based amphiphile; sugar motifs are often recognition binding moieties and these liposomes may be able to target specific cells, such as cancer cells, c) that the combination of the exceptional impermeability, a controlled stimulus response, and a smart surface grants an interesting potential for these nanocarriers for liposomal delivery of challenging drugs.