Understanding and exploiting lipid interactions

我们的研究项目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，并开发新的仿生技术。*一些多肽和一些蛋白质可以诱导脂质从膜上外流；这种现象在精子成熟和胆固醇反向运输等生物过程中发挥核心作用。尽管这些脂质外流是最重要的，但其机制在分子水平上尚不清楚。为了更好地理解这些过程，我们将描述洗涤剂、多肽或蛋白质诱导的从模型膜中提取脂类的特征，以确定决定从膜中提取特定脂质的关键相互作用。角质层(SC)的脂类是皮肤不通透性的主要原因。角质层(SC)是表皮的顶层。这种特殊的屏障与其相当大比例的脂类形成的不同寻常的晶相有关。最近，我们发现这种基质可能包括碳氢纳米滴，这一假设可能会导致我们重新考虑对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体/液体基质所需的分子参数，并评估固体/液体平衡在皮肤非渗透性中的作用。对SC脂类自组装的了解将有助于维持健康的皮肤屏障，并有可能改变经皮给药的屏障。我的团队正在开发一种由单烷基两亲性和甾醇形成的脂质体的新平台，并显示出独特的性质，包括非常低的渗透性和在恶劣环境中非常好的稳定性。在下一个授权期，我们建议：1)表征关键的双分子过程，如脂质触发和胆固醇氧化；这些发现将有助于设计改进的纳米载体，并可能为理解一些生物学过程提供新的概念；b)研究使用糖基两亲分子制备非磷脂脂质体的可能性；糖基序通常是识别结合部分，这些脂质体可能能够靶向特定的细胞，如癌细胞；c)异常的不通透性、可控的刺激反应和智能表面的组合赋予这些纳米载体以脂质体输送具有挑战性药物的有趣潜力。

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.