Biomimetic Proteolipid Multilayers – Structure and Properties

In order to fully understand biological phenomena, one must obtain detailed information on the structure and function of biomolecules. Proteins are large molecules that can also be considered to be biological nanoparticles. This project focuses on specific biological structures: molecular multilayers made of lipid and protein. One such structure is the myelin sheath in the nervous system, which is important for the normal conduction of nerve impulses. Myelin enables rapid nerve impulses along the neuronal axon, and the breakdown of the myelin structure is linked to chronic neurological diseases, such as multiple sclerosis. We will study the molecular structure of myelin at different levels of detail, using modern multidisciplinary methods and large-scale international research infrastructures. The expected results will range from structures of individual protein molecules at the atomic level to the physicochemical properties, structure, and dynamics of multilayered biomolecular structures. The results from this basic research project will provide an unprecedented view into multilayers made of protein and lipid in biological systems, specifically focusing on the molecular details of myelin. They will both enable a better understanding of the structure and function of the vertebrate nervous system and shed light on the molecular mechanisms of chronic demyelinating disease in humans.

Biological membranes are organized assemblies of protein and lipid molecules. But how exactly do such tightly controlled biostructures form at the molecular level? How do the individual molecules interact; is there synergy/competition? My model system is myelin, a tightly packed proteolipid multilayer, which is important for the normal functioning of the vertebrate nervous system. This proposal will cover new avenues of fundamental research on proteolipid biomembranes, especially ones that form spontaneous multilayers. I will provide information on the assembly of biomolecular supracomplexes and proteolipid membrane multilayers. The project will range from the molecular to the supramolecular level (from the nano to the meso scale) and focus on both structure and dynamics of the system. High-resolution structural and dynamical studies on myelin-like multilayers (“artificial myelin”), as well as the detailed molecular steps involved in their assembly, will be carried out with various techniques. These studies will provide an unprecendented view into the molecular structure and properties of the myelin sheath and possible mechanisms of eventual demyelinating disease. The results can be used to further understand other biological systems relying on the formation of ordered 3D assemblies of protein and lipid. As a specific case, the results will shed light on the molecular mechanisms of human demyelinating disease.