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

软材料和生物材料的一个决定性方面是它们对各种干扰影响的反应程度。我提出的项目的三个互补目标旨在更好地理解自组装软材料，特别是脂质组装和可变形胶体，如何在压力、温度或分子扰动的变化下重组。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。脂类分子具有水溶性头部和油性链。在水中，它们自我组装成迷人而重要的结构，比如细胞膜下面的双层结构。重组脂质组装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，表面活性剂层在肺部空气-水界面的扩散，以及具有特定结构特性的抗菌多肽（amp）对细菌膜的破坏。合成的例子包括“二束”脂质混合物，在这种混合物中，链长不匹配的脂质分离导致小颗粒在加热时逐渐凝聚成更大的结构。**研究不同压力下的软质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分子层来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。通过研究高压下的双细胞分散体，我们将探索像链交错凝胶这样的新相是如何从脂质性质的不匹配中产生的。这些研究将采用一种独特的变压氘核磁共振探针。**我们的第二个目标是更好地理解多肽如何驱动脂质组装重组。我们将与生物化学方面的合作伙伴一起，利用核磁共振直接观察抗菌肽（AMPs）对含有氘标记成分的细菌膜的影响。通过控制pH，我们还将研究来自cod的新型amp的膜扰动能力和取向如何随着肽电荷的变化而变化。**在肺中，基本的表面活性剂功能依赖于小蛋白质，通过适当结构的桥，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，具有丰富的行为，在分子水平上尚未完全理解。微凝胶经历崩溃转变，伴随着大规模的水释放，有许多潜在的应用，包括药物输送。我们的第三个目标是利用可变压力核磁共振，与纪念大学和瑞典隆德大学的同事合作，研究这种材料中的聚合物运动，并通过崩溃转变表征局部结构。**除了增强我们对软质材料重组过程的理解外，该项目还将有助于推进诸如改善呼吸问题的人工肺表面活性剂疗法、减轻获得性抗生素耐药性的抗菌肽和药物递送策略（脂质体封装、胶体捕获）等技术的发展。新的方面包括使用双层胶束聚结来模拟生物双层重建，将氘标签插入胶体和细菌系统，以及使用变压核磁共振分析软物质。

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.