How Interfacial Structure and Organization Govern Biological and Material Functionality

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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.