Proteins and Lipids
Proteins are the molecular machinery of life, tirelessly active in every cell to transport, synthesize, divide, and transform substances. Their function is determined by the sequence of amino acids and their three-dimensional arrangement, as well as structural rearrangements influenced by environmental conditions. Many proteins exhibit intrinsic disorder, showing conformational properties similar to polymers, making their dynamics and interactions well-suited for techniques developed for polymers [1].
Biological membranes, composed of a phospholipid bilayer, separate cells or create intracellular compartments, controlling substance entry and exit. Membranes and their proteins are crucial for trafficking, transport, and are involved in health and disease. Special lipid mixtures can self-assemble into structures resembling cell membranes, allowing the study of protein interactions and transport phenomena without the need of whole cells.
Neutron scattering methods enable the examination of biological structures’ dynamics and structure. Biological samples can be studied in D2O buffer solution, close to their natural state, without radiation damage. Small Angle Scattering (SAXS/SANS) determines biomolecular structures in solution. Neutron Spin Echo Spectroscopy (NSE) investigates large-scale movements on the 1 to 200 nanosecond timescale, determining relaxation time and motion amplitude [2]. Quasi-elastic scattering methods like time of flight (TOF) or backscattering (BS) examine sub-nanosecond timescale motions of amino acid sidechains or hydrogens. Neutron protein crystallography locates hydrogen atoms even at moderate resolutions of 2 Å.
Myelin, primarily composed of phospholipids, plays a crucial role in the transmission of signals between neurons. Recent advancements have enabled the mapping of concentrations, directions, and structural parameters of nerve fiber connections within the brain. We utilize 3D-scanning SAXS/SANS [3] to study the impact of various pathologies on the brain comprehensively. This technique allows us to examine brain slices across multiple length scales, ranging from nanometers to centimeters. In collaboration with our partners at IBI-1, we are working to integrate the established 3D-PLI methods with our findings.
[1] L. R. Stingaciu, R. Biehl, D. Changwoo, D. Richter, and A. M. Stadler,
Reduced Internal Friction by Osmolyte Interaction in Intrinsically Disordered Myelin Basic Protein
J. Phys. Chem. Lett. 11, 292 (2020)
[2] R. Biehl, M. Monkenbusch, and D. Richter, Soft Matter 7, 1299 (2011)
Exploring internal protein dynamics by neutron spin echo spectroscopy
Soft Matter 7, 1299 (2011)
[3] Maiti, S., Frielinghaus, H., Gräßel, D. et al.
Distribution and orientation of nerve fibers and myelin assembly in a brain section retrieved by small-angle neutron scattering.
Sci Rep 11, 17306 (2021). https://doi.org/10.1038/s41598-021-92995-2