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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=567746
• 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反应程度。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，特别是脂类组件和可变形胶体是如何随着压力或温度的变化或分子扰动进行重组的。我的团队使用固态核磁共振(核磁共振)通过其组成分子的运动来表征软材料。脂类分子有水溶头和油链。在水中，它们自组装成吸引人的重要结构，就像细胞膜下面的双层一样。重组脂类集合的过程在生物学和软材料科学中都很重要。例子包括膜融合，肺内空气-水界面表面活性物层的铺展，以及具有特定结构特性的抗菌多肽(AMPs)对细菌膜的破坏。人工合成的例子包括脂类的“双胞”混合物，在这种混合物中，具有不匹配链长的脂类的分离会导致小颗粒在受热时逐渐结合成更长的结构。研究不同压力下的软材料可以分离温度和分子堆积的影响。一个项目目标是通过观察压力如何影响双层，了解具有不同性质的分子之间的相互作用如何决定脂质组装组织。通过研究不同压力下的脂-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。通过研究高压下的双细胞分散，我们将探索新的相，如链状交错指状凝胶，是如何由脂类性质的不匹配造成的。这些研究将使用一种独特的变压氢核磁共振探头。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。与一位生物化学的合作者一起，我们将使用核磁共振技术直接观察抗菌肽(AMPs)对带有氚标记成分的细菌膜的影响。通过控制pH，我们还将研究来自鳕鱼的新型AMP的膜扰动能力和取向如何随肽电荷的变化而变化。在肺中，基本的表面活性物质的功能依赖于小蛋白，这些小蛋白通过适当结构的桥梁帮助脂层之间的物质转移。我们将在模型系统中通过观察来自肺表面活性物质的特定多肽如何影响双层胶束合并成更大的结构来研究这种过程。微凝胶是一种可变形的交联型聚合物胶体，其丰富的行为在分子水平上还没有被完全理解。随着水的大规模释放，经历崩塌转变的微凝胶有许多潜在的应用，包括药物输送。我们的第三个目标是与瑞典纪念大学和隆德大学的同事合作，使用可变压力核磁共振来研究此类材料中的聚合物运动，并通过坍塌转变来表征局部结构。除了增强我们对软材料重组过程的理解外，该项目还将帮助推进技术进步，如改进的人工肺表面活性物质治疗呼吸问题、减少获得性抗生素耐药性的AMP以及药物输送策略(脂质体包裹、胶体捕获)。新的方面包括使用双层胶束聚合来模拟生物双层重建，在胶体和细菌系统中插入氚标记，以及使用可变压力核磁共振来研究软物质。