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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748448
• 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/或合成的脂质构建包含朗缪尔单层、脂质体和支撑的脂质双层/单层的模型膜。我们试图了解它们的“体积”性质，如机械稳定性、弹性、流动性是如何被微米和纳米尺度的结构所控制的，反过来又是如何被复杂的分子相互作用和分子构象所控制的。我们利用这些知识来探索覆盖在眼睛表面的脂质膜是如何发挥作用的，以及当眼睛表面暴露于污染物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物理变化，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（AMP）的序列-结构-功能关系，这些抗菌肽被吹捧为潜在的新抗生素，可以避免或至少减缓细菌耐药性的发展。随着越来越多的多重耐药细菌的出现，化学家必须将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：AMP通过靶向和破坏细菌细胞壁提供了这种可能性。一方面，我们试图破坏细菌的细胞膜，另一方面，我们试图从它们身上学习。Ladderane脂质来自一类表现出极端膜不渗透性和稳定性的细菌。我们将研究这些脂质，以了解这些性质是如何从这些含有高度不寻常结构的脂质中获得的。如果我们能了解这些结构如何控制膜渗透性，然后我们可以使用这些脂质作为添加剂，例如在脂质体制剂中，以改善它们的寿命和保存期，脂质体也可用于包覆纳米颗粒以产生赋予生物相容性的功能性薄膜涂层，同时还提供包封活性物质的手段。成分.我们已经开发出一种方法来控制膜渗透性与脂质，改变构象后，暴露于某些波长的光（原位产生的纳米粒子）。我们将研究脂质涂层的组成对于控制释放的活性剂的量的重要性，以及是否可以通过添加模拟细菌的脂质结构来改善这一点。我们还将把我们的新型AMP嵌入到双层膜中，这样它们的释放就可以被光触发。从长远来看，可以设想开发用于治疗持续性皮肤或伤口感染等应用的新型纳米材料。总的来说，这个项目旨在利用膜结构的物理和化学知识来设计生物应用材料。