Molecular Structure and Dynamics of Membranes

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The determination of molecular structure and dynamics in biological materials is one of the greatest challenges in modern biophysics, in particular under physiological conditions. Few experimental techniques can access structural and dynamical properties on the nanometer scale. We will use advanced X-ray and neutron scattering techniques as powerful tools to study structure, dynamics and interactions in synthetic membranes and biomaterials down to nanometer length scales and up to nanosecond times. In the proposed research project we will study the interaction of membrane-active molecules and peptides with model lipid membranes, their organization within the lipid bilayer and their impact on the lipid matrix. The experiments will be conducted in our Laboratory for Membrane and Protein Dynamics at McMaster, the Canadian Neutron Beam Centre at Chalk River Laboratories and international neutron sources in the US and Europe. The formation of rafts in the presence of cholesterol is currently an important topic in membrane biophysics. We will study formation and properties of rafts as function of membrane composition and in the presence of molecules, such as acetylsalicylic acid (ASA), using a new technique, namely coherence length dependent neutron diffraction. This new technique is capable to detect small, nanometer sized and transient domains in membranes and ideally suited to study nature and properties of these rafts. The molecular structure and dynamics of membranes containing ethanol will be studied to better understand the molecular processes involved in trans-membrane diffusion and functioning of anesthetics. By using deuterium labeling and inelastic neutron scattering, the precise location and lateral and trans-membrane dynamics of ethanol and water molecules will be determined. These will be the first experiments of this kind and important to understand ethanol’s effect on transport and membrane organization. Depending on size and hydrophilic and hydrophobic properties, small molecules can be incorporated in the hydrophobic membrane core, partition in the lipid head group region or be confined between neighbouring bilayers in the stack. We will study the interaction and organization of nucleotides, ASA and ibuprofen molecules when in contact with lipid membranes and their impact on the lipid matrix. These molecules are excellent model system to investigate basic properties, interactions and organization of small molecules of different properties in lipid membranes. Our main objective is the lateral organization of these molecules. For ASA and nucleotides we will provide unprecedented structural information. Macroscopic properties of biomaterials are often determined by the organization of their elementary building blocks, such as proteins, chitin and keratin, into secondary structures. We will study biomaterials, such as protein fibres, squid pens and bug shells and hair, to study the organization of these molecules into beta-sheets, nano-crystallites and nano-fibrils in-situ. Using our advanced X-ray setup, we will obtain quantitative information about the organization of the biomolecules in different secondary structures and structural parameters, which is essential to relate molecular organization to macroscopic function. These projects are important steps towards the determination of molecular structure and dynamics of membranes and biological macromolecules in-situ, in their relevant, disordered state in their ‘natural’ environment, and of general interest to the soft-matter and biophysical community.