Phase behaviour, reorganization, and dynamics of lipid and soft matter assemblies

脂质和软物质组装体的相行为、重组和动力学

• 批准号: RGPIN-2014-06345
• 负责人: Morrow, Michael
• 金额: $ 2.11万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612172
• 关键词: Phase; behaviour; reorganization; dynamics; lipid

One defining aspect of soft and biological materials is the extent to which they respond to various perturbing influences. The three complementary objectives of my proposed program aim at gaining a better understanding of how self-assembled soft materials, particularly lipid assemblies and deformable colloids, reorganize in response to changes in pressure or temperature or to molecular perturbations. My group uses solid-state nuclear magnetic resonance (NMR) to characterize soft materials via motions of their component molecules. Lipids molecules have water-soluble heads and oily chains. In water they self-assemble into fascinating and important structures like the bilayers underlying cell membranes. Processes that reorganize lipid assemblies are important both in biology and in soft materials science. Examples include membrane fusion, the spreading of a surfactant layer at air-water interfaces in lungs, and bacterial membrane disruption by antimicrobial polypeptides (AMPs) with specific structural properties. Synthetic examples include “bicellar” mixtures of lipids in which separation of lipids with mismatched chain-lengths results in small particles that progressively coalesce into more extended structures on heating. Studying soft materials at different pressures can separate effects of temperature and molecular packing. One program objective is to understand how interactions between molecules with different properties determine lipid assembly organization by observing how pressure affects bilayers. By studying lipid-cholesterol mixtures at different pressures, we will compare effects, on mixture properties, of interactions at the bilayer surface and in its interior. By studying bicellar dispersions at high pressure, we will explore how novel phases, like chain-interdigitated gel, result from a mismatch of lipid properties. These studies will employ a unique variable-pressure deuterium NMR probe. Our second objective is to better understand how polypeptides can drive lipid assembly reorganization. With a collaborator in Biochemistry, we will use NMR to directly observe effects of antimicrobial peptides (AMPs) on bacterial membranes with deuterium-labeled components. By controlling pH, we will also study how the membrane-perturbing capacities and orientations of novel AMPs, from cod, change with peptide charge. In lungs, the essential surfactant function depends on small proteins that help transfer material, via appropriately structured bridges, between lipid layers. We will study such processes in model systems by observing how specific peptides, derived from lung surfactant, affect the merging of bilayered micelles into larger structures. Microgels are deformable cross-linked polymer colloids with rich behaviours not fully understood at the molecular level. Microgels that undergo a collapse transition, along with a large-scale release of water, have many potential applications including drug delivery. Our third objective is to use variable-pressure NMR, in collaboration with colleagues at Memorial and at Lund University, Sweden, to study polymer motions in such materials and to characterize local structure through the collapse transition. Along with enhancing our understanding of processes that can reorganize soft materials, this program will help advance technologies like improved artificial lung surfactant therapies for respiratory problems, AMPs to mitigate acquired antibiotic resistance, and drug delivery strategies (liposome encapsulation, colloidal trapping). Novel aspects include the use of bilayered micelle coalescence to model biological bilayer reconstruction, the insertion of deuterium labels into colloidal and bacterial systems, and the use of variable-pressure NMR for soft matter.

软材料和生物材料的一个定义方面是它们对各种扰动影响的响应程度。我提出的计划的三个互补目标旨在更好地了解自组装软材料，特别是脂质组件和可变形胶体，如何响应压力或温度变化或分子扰动而重组。我的团队使用固态核磁共振（NMR）通过其组成分子的运动来表征软材料。 脂质分子有水溶性的头部和油性链。在水中，它们自我组装成迷人而重要的结构，如细胞膜下的双层。重组脂质组装的过程在生物学和软材料科学中都很重要。实例包括膜融合、表面活性剂层在肺中的空气-水界面处的扩散以及具有特定结构特性的抗菌多肽（AMP）对细菌膜的破坏。合成实例包括脂质的“双胞”混合物，其中具有不匹配链长的脂质的分离导致小颗粒在加热时逐渐聚结成更延伸的结构。 研究不同压力下的软材料可以区分温度和分子堆积的影响。一个程序的目标是了解不同性质的分子之间的相互作用如何通过观察压力如何影响双层来确定脂质组装组织。通过研究不同压力下的脂质-胆固醇混合物，我们将比较双层表面和内部相互作用对混合物性质的影响。通过研究在高压下的双胞分散体，我们将探索如何新的阶段，如链交叉凝胶，导致脂质性质的不匹配。这些研究将采用独特的变压氘NMR探头。 我们的第二个目标是更好地了解多肽如何驱动脂质组装重组。与生物化学的合作者，我们将使用NMR直接观察抗菌肽（AMP）对具有氘标记组分的细菌膜的影响。通过控制pH值，我们还将研究如何膜扰动能力和新的AMP的方向，从鳕鱼，肽电荷的变化。 在肺中，基本的表面活性剂功能取决于小蛋白质，这些小蛋白质通过适当结构的桥梁在脂质层之间帮助转移物质。我们将通过观察来自肺表面活性剂的特定肽如何影响双层胶束合并成更大的结构来研究模型系统中的这些过程。 微凝胶是可变形的交联聚合物胶体，具有在分子水平上尚未完全理解的丰富行为。微凝胶经历塌陷转变，沿着大规模释放水，具有许多潜在的应用，包括药物递送。我们的第三个目标是使用变压核磁共振，与同事在纪念和隆德大学，瑞典，研究聚合物在这种材料中的运动，并通过崩溃过渡的本地结构的特点。 沿着增强我们对可重组软材料的过程的理解，该计划将有助于推进技术，如用于呼吸问题的改进型人工肺表面活性剂疗法、减轻获得性抗生素耐药性的AMP以及药物递送策略（脂质体包封、胶体捕获）。新的方面包括使用双层胶束聚结模型生物双层重建，插入氘标记到胶体和细菌系统，和使用变压NMR软物质。