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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739276
• 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。模型膜包括Langmuir单层，脂质体和支持脂质双层/单层，由纯化和/或合成脂质构建。我们试图了解它们的“体积”特性，如机械稳定性、弹性、流动性是如何由微米和纳米级结构控制的，反过来，这些特性又是如何由复杂的分子相互作用和分子构象控制的。我们利用这些知识来探索覆盖眼睛表面的脂质膜是如何起作用的，以及当眼睛表面暴露于污染物时发生了什么物理或化学变化。我们的目标是了解干眼症背后的生理变化，并开发添加剂来预防或减少污染损害。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，抗菌肽被吹捧为可能逃避或至少减缓细菌耐药性发展的潜在新型抗生素。随着越来越多的多重耐药细菌的出现，化学家们必须将注意力转向开发新型抗生素，这些抗生素通过全新的机制起作用：amp通过靶向和破坏细菌细胞壁提供了这种可能性。一方面，我们试图破坏细菌膜，另一方面，我们试图向他们学习。Ladderane脂类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脂质中产生的，这些脂质包含了非常不寻常的结构。如果我们能够理解这些结构是如何控制膜渗透性的，那么我们就可以将这些脂质用作添加剂，例如在脂质体配方中，以提高它们的使用寿命和保质期。脂质体也可以用来包裹纳米颗粒，形成具有生物相容性的功能性薄膜涂层，同时也提供了一种封装活性成分的方法。我们已经开发出一种控制膜通透性的方法，通过脂质在暴露于特定波长的光（由纳米颗粒原位产生）时改变构象。我们将研究脂质涂层的组成对控制活性剂释放量的重要性，以及是否可以通过添加模仿细菌的脂质结构来改善这一点。我们还将把新的amp嵌入到双层中，这样它们的释放就可以由照片触发。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。总体而言，本课程旨在利用膜结构的物理和化学知识来设计生物应用材料。