How Interfacial Structure and Organization Govern Biological and Material Functionality

界面结构和组织如何控制生物和材料功能

• 批准号: RGPIN-2019-07043
• 负责人: DeWolf, Christine
• 金额: $ 2.11万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716088
• 关键词: How; Interfacial; Structure; Organization; Govern

This program uses a surface chemistry approach to characterize the biophysical properties of biological membranes. Model membranes comprising Langmuir monolayers, liposomes and supported lipid bilayers/monolayers are constructed from purified and/or synthetic lipids. We seek to understand how their "bulk" properties such as mechanical stability, elasticity, fluidity are controlled by micron and nanometer scale structures and in turn how these are governed by complex sets of molecular interactions and molecular conformations. We use this knowledge to probe how the lipid film covering the eye surface functions and what physical or chemical changes occur when the eye surface is exposed to pollutants. We aim to understand the physical changes behind dry-eye syndrome and develop additives to prevent or minimize pollution damage. We also use these approaches to understand the sequence-structure-function relationships of antimicrobial peptides (AMPs), touted as potential new antibiotics that may evade or at least slow the development of bacterial resistance. With many more multi-drug resistant bacteria emerging, chemists must direct their attention to the development of new classes of antibiotics that work by completely new mechanisms: AMPs offer that possibility by targeting and disrupting the bacterial cell wall. On one hand we seek to destroy bacterial membranes, on the other hand we seek to learn from them. Ladderane lipids come from a class of bacteria that exhibit extreme membrane impermeability and stability. We will study these lipids to understand how these properties derive from these lipids which comprise highly unusual structures. If we can understand how these structures control membrane permeability, we can then employ these lipids as additives for example in liposome formulations to improve their longevity and shelf-life. Liposomes can also be used to coat nanoparticles to create functional thin film coatings that confer biocompatibility while also offering a means to encapsulate active ingredients. We have developed a way to control membrane permeability with a lipid that changes conformation upon exposure to certain wavelengths of light (produced in situ by the nanoparticle). We will study the importance of the composition of the lipid coating for controlling the amount of active agent released and whether this can be improved by adding lipid structures that mimic those from bacteria. We will also look to embed our new AMPs in the bilayer such that their release could be photo-triggered. In the long term the development of new nanomaterials for applications such as the treatment of persistent skin or wound infections can be envisaged. Overall, this program seeks to use a physical and chemical knowledge of membrane structure to design materials for bioapplications.

该程序使用表面化学方法来表征生物膜的生物物理特性。由纯化的和/或合成的脂类构建包含朗缪尔单分子层、脂质体和支撑的脂类双分子层/单分子膜的模型膜。我们试图了解它们的机械稳定性、弹性、流动性等“大块”性质是如何由微米和纳米级结构控制的，进而又是如何由复杂的分子相互作用和分子构象控制的。我们利用这一知识来探索覆盖在眼睛表面的脂膜是如何发挥作用的，以及当眼睛表面暴露在污染物中时，会发生什么物理或化学变化。我们的目标是了解干眼综合征背后的生理变化，并开发添加剂来防止或最大限度地减少污染损害。我们还使用这些方法来了解抗菌肽(AMPs)的序列-结构-功能关系，抗菌肽被吹捧为潜在的新抗生素，可能避免或至少减缓细菌耐药性的发展。随着更多耐多药细菌的出现，化学家们必须将他们的注意力集中在开发通过全新机制发挥作用的新型抗生素上：AMPS通过靶向和破坏细菌细胞壁提供了这种可能性。一方面，我们寻求破坏细菌膜，另一方面，我们寻求向它们学习。Ladderane类脂来自一类表现出极强的膜不通透性和稳定性的细菌。我们将研究这些脂类，以了解这些性质是如何从这些包含非常不寻常的结构的脂类中获得的。如果我们能够了解这些结构是如何控制膜通透性的，那么我们就可以将这些脂类用作添加剂，例如在脂质体配方中，以提高它们的寿命和货架期。脂质体还可以用来包裹纳米颗粒，以创建具有生物兼容性的功能性薄膜涂层，同时还提供了一种封装活性成分的方法。我们已经开发出一种方法，通过一种脂类来控制膜的通透性，这种脂类在暴露于特定波长的光(由纳米颗粒原位产生)时改变构象。我们将研究脂类涂层的组成对控制活性物质释放量的重要性，以及是否可以通过添加模仿细菌的脂类结构来改善这一点。我们还将寻求在双层中嵌入我们的新AMP，这样它们的释放可以是光触发的。从长远来看，开发新的纳米材料用于治疗持续性皮肤或伤口感染是可以预见的。总体而言，这个项目寻求使用膜结构的物理和化学知识来设计生物应用材料。