Peptide-induced reorganization of lipid assemblies

脂质分子有水溶性的头和油性的尾。它们聚集成双层结构，如细胞膜，多层结构，如肺表面活性剂和胶束。许多生物过程涉及具有特定结构和电荷分布的蛋白质或多肽对脂质组装的重组。例如，特殊的蛋白质能够在肺的空气-水界面形成脂质层，从而允许肺膨胀和呼吸。其他多肽帮助生物体抵抗细菌感染。我们将研究脂质-肽相互作用如何促进脂质组装重组：(1)表面活性剂层在肺部空气-水界面的扩散；(2)抗菌肽（AMPs）对细菌膜的破坏。我们还将研究(3)“活性”脂质颗粒系统中的非平衡行为。我们将使用核磁共振（NMR），光散射和量热法来研究肽诱导的脂质组装和完整细菌膜的结构和运动的变化。固态核磁共振表明，一些肺表面活性剂蛋白促进交叉，从对立的单层脂链穿过双层中层，形成薄而有序的层。因此，交错作用可能是表面活性剂物质在空气-水界面和多层储层之间传递的重要步骤。目的(1)是通过构建含有蛋白质片段的模型脂质系统的温度-组成相图，了解特定的蛋白质结构元件如何促进表面活性剂的扩散，这些蛋白质片段被选择用于促进表面活性剂的重组，包括交叉化。研究对象(1)对表面活性剂缺乏引起的严重呼吸系统疾病的新治疗方法的发展具有启示意义。与V. Booth（生物化学）合作，我们成功地将氘添加到细菌膜上，并使用2H NMR研究了AMPs对膜的扰动以及某些细菌刚性外壁变薄的影响。目的（2a）将研究干扰其他细菌中存在的外脂多糖层如何改变AMP对其内外膜的作用。目的（2b）将了解心磷脂（CL）是一种细菌和线粒体膜脂，具有四个酰基链和ph依赖电荷，如何影响其含量丰富的膜的物理性质。2H核磁共振将用于构建相图和研究脂质运动在选定的含cl模型膜。研究对象(2)对开发控制耐药细菌的新策略具有启示意义。在与a . Yethiraj的合作中，目标(3)将把细菌视紫红质（一种光激活质子泵）嵌入纳米级脂质单胞体中，用于研究活性粒子的非平衡运动。该计划旨在将软物质相互作用与生物功能联系起来，并为潜在的治疗相关性提供见解。

Lipid molecules have water-soluble heads and oily tails. They assemble into bilayers, as in cell membranes, multilayers, as in lung surfactant, and micelles. Many biological processes involve reorganization of lipid assemblies by proteins or polypeptides with specific structures and charge distributions. For example, special proteins enable formation of a lipid layer, at the lung air-water interface, that permits lung inflation and thus breathing. Other polypeptides help organisms resist bacterial infection. We will study how lipid-peptide interactions promote lipid assembly reorganization in: (1) the spreading of surfactant layers at the air-water interface in lungs and (2) disruption of bacterial membranes by antimicrobial peptides (AMPs). We will also study (3) non-equilibrium behaviour in systems of "active" lipid particles. We will use nuclear magnetic resonance (NMR), light scattering, and calorimetry to study peptide-induced changes in the structures and motions of lipid assemblies and intact bacterial membranes. Solid state NMR has shown that some lung surfactant proteins promote interdigitation, the intermingling of lipid chains from opposing monolayers across the bilayer mid-plane to give thin, ordered layers. Interdigitation might thus be an important step in the transfer of surfactant material between the air-water interface and multilayer reservoirs. Object (1) is to learn how specific protein structural elements contribute to surfactant spreading by building temperature-composition phase diagrams for model lipid systems containing protein fragments selected for their capacity to promote surfactant reorganization including interdigitation. Object (1) has implications for the development of new treatments for serious respiratory conditions resulting from surfactant deficiency. In collaboration with V. Booth (Biochemistry), we successfully added deuterium to bacterial membranes and used 2H NMR to study membrane perturbation by AMPs and the effects of thinning the rigid outer walls of some bacteria. Object (2a) will be to study how perturbing the outer lipopolysaccharide layer present in other bacteria alters AMP effects on their inner and outer membranes. Object (2b) will be to learn how cardiolipin (CL), a bacterial and mitochondrial membrane lipid with four acyl chains and a pH-dependent charge, affects physical properties of membranes in which it is abundant. 2H NMR will be used to construct phase diagrams and study lipid motions in selected CL-containing model membranes. Object (2) has implications for the development of new strategies to control antibiotic-resistant bacteria. In collaboration with A. Yethiraj, object (3) will be to embed bacteriorhodopsin, a photoactivated proton pump, into nanoscale lipid bicelles which will be used to study non-equilibrium motion of active particles. This program aims to relate soft matter interactions to biological function and contribute insights with potential therapeutic relevance.