Understanding and exploiting lipid interactions

我们的研究计划旨在表征涉及脂质的生物材料的结构和动力学，以了解关键生物事件的机制，并开发新的仿生学。*某些多肽和蛋白质可诱导脂质从细胞膜外排；这种现象在精子成熟和胆固醇逆向转运等生物过程中起着核心作用。尽管这些脂质外溢的首要重要性，其机制尚不了解在分子水平。我们将表征洗涤剂、肽或蛋白质诱导的从模型膜中提取脂质，以定义决定从膜中提取特定脂质的关键相互作用，以便更好地理解这些过程。角质层（表皮的顶层）的脂质在很大程度上负责皮肤的不渗透性。这种特殊的屏障与由相当比例的脂质形成的不寻常的晶体相有关。最近，我们发现这种基质可能包括碳氢化合物纳米液滴，这一假设可能会导致我们重新考虑我们对SC结构/功能的理解。我们将继续研究SC模型的结构和动力学，以确定形成这种独特的固/液基质所需的分子参数，并评估固/液平衡在皮肤抗渗性中的作用。由此产生的对SC脂质自组装的理解将有助于维持健康的皮肤屏障，并有可能改变经皮药物传递的屏障。*我的团队正在开发一种新的脂质体平台，由单烷基化两亲体和甾醇组成，并显示出独特的性能，包括极低的渗透性和在恶劣环境下的良好稳定性。在下一个授权期内，我们建议i)表征关键的双分子层过程，如脂质翻转和胆固醇氧化；这些发现将有助于设计改进的纳米载体，并可能为理解某些生物过程提供新的概念b)检查使用糖基两亲体制造非磷脂脂质体的可能性；糖基元通常是识别结合部分，这些脂质体可能能够靶向特定细胞，如癌细胞，c)特殊的不渗透性，受控的刺激反应和智能表面的组合为这些纳米载体提供了一个有趣的潜力，用于脂质体递送具有挑战性的药物。

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.