Grant: Discovery Grants Program - Individual

Lipid molecules have water-soluble heads and oily tails. They assemble into bilayers, as in cell membranes, multilayers, as in lung surfactant, and micelles. Many biological processes involve reorganization of lipid assemblies by proteins or polypeptides with specific structures and charge distributions. For example, special proteins enable formation of a lipid layer, at the lung air-water interface, that permits lung inflation and thus breathing. Other polypeptides help organisms resist bacterial infection. We will study how lipid-peptide interactions promote lipid assembly reorganization in: (1) the spreading of surfactant layers at the air-water interface in lungs and (2) disruption of bacterial membranes by antimicrobial peptides (AMPs). We will also study (3) non-equilibrium behaviour in systems of "active" lipid particles. We will use nuclear magnetic resonance (NMR), light scattering, and calorimetry to study peptide-induced changes in the structures and motions of lipid assemblies and intact bacterial membranes. Solid state NMR has shown that some lung surfactant proteins promote interdigitation, the intermingling of lipid chains from opposing monolayers across the bilayer mid-plane to give thin, ordered layers. Interdigitation might thus be an important step in the transfer of surfactant material between the air-water interface and multilayer reservoirs. Object (1) is to learn how specific protein structural elements contribute to surfactant spreading by building temperature-composition phase diagrams for model lipid systems containing protein fragments selected for their capacity to promote surfactant reorganization including interdigitation. Object (1) has implications for the development of new treatments for serious respiratory conditions resulting from surfactant deficiency. In collaboration with V. Booth (Biochemistry), we successfully added deuterium to bacterial membranes and used 2H NMR to study membrane perturbation by AMPs and the effects of thinning the rigid outer walls of some bacteria. Object (2a) will be to study how perturbing the outer lipopolysaccharide layer present in other bacteria alters AMP effects on their inner and outer membranes. Object (2b) will be to learn how cardiolipin (CL), a bacterial and mitochondrial membrane lipid with four acyl chains and a pH-dependent charge, affects physical properties of membranes in which it is abundant. 2H NMR will be used to construct phase diagrams and study lipid motions in selected CL-containing model membranes. Object (2) has implications for the development of new strategies to control antibiotic-resistant bacteria. In collaboration with A. Yethiraj, object (3) will be to embed bacteriorhodopsin, a photoactivated proton pump, into nanoscale lipid bicelles which will be used to study non-equilibrium motion of active particles. This program aims to relate soft matter interactions to biological function and contribute insights with potential therapeutic relevance.