Peptide-induced reorganization of lipid assemblies

脂质分子有水溶性的头部和油性的尾部。它们组装成双层（如细胞膜）、多层（如肺表面活性剂）和胶束。许多生物过程涉及通过具有特定结构和电荷分布的蛋白质或多肽重组脂质组装体。例如，特殊的蛋白质能够在肺空气-水界面形成脂质层，从而允许肺充气并因此呼吸。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）肺中空气-水界面表面活性剂层的扩散和（2）抗菌肽（AMP）对细菌膜的破坏。我们还将研究（3）“活性”脂质颗粒系统的非平衡行为。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体和完整细菌膜的结构和运动变化。固态NMR显示，一些肺表面活性蛋白促进交错，即来自相对单层的脂质链穿过双层中平面的混合，以产生薄的有序层。因此，交错可能是一个重要的步骤，在空气-水界面和多层油藏之间的表面活性剂材料的转移。目的（1）是了解特定的蛋白质结构元件如何有助于表面活性剂的传播，通过建立温度-组成相图模型脂质系统含有蛋白质片段选择其能力，以促进表面活性剂重组，包括叉指。目的（1）对开发治疗表面活性物质缺乏引起的严重呼吸系统疾病的新疗法具有意义。在与V. Booth（生物化学）的合作中，我们成功地将氘添加到细菌膜中，并使用2 H NMR研究AMP对膜的扰动以及一些细菌刚性外壁变薄的影响。目的（2a）将研究如何扰乱其他细菌中存在的外脂多糖层，改变AMP对它们的内膜和外膜的影响。目的（2b）将了解心磷脂（CL），一种具有四个酰基链和pH依赖性电荷的细菌和线粒体膜脂质，如何影响其丰富的膜的物理性质。2 H NMR将用于构建相图和研究选定的含CL模型膜中的脂质运动。目的（2）对控制耐药细菌的新策略的发展具有启示意义。与A合作。Yethiraj，目标（3）将是将细菌视紫红质（一种光活化的质子泵）嵌入纳米级脂质胶束中，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，并提供具有潜在治疗意义的见解。

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.