From: 2023-06-13 14:00 to 15:00
Place: LINXS (Scheelvägen 19, Lund), with digital participation possibility (Zoom)
Contact: anna [dot] stradner [at] fkem1 [dot] lu [dot] se

LINXS Guest Seminar with Andreas Stadler (JCNS) on neutron scattering studies of myelin basic proteins.

When: June 13, 14:00–15.00
Where: at LINXS (Scheelvägen 19, Lund), with digital participation possibility (Zoom).
Title: Neutron scattering studies on myelin basic protein and its interactions with biomimetic myelin membranes
Speaker: Andreas Stadler, Jülich Centre for Neutron Science (JCNS)

Abstract: Myelin basic protein (MBP) and its interaction with lipids of the myelin sheath plays a crucial role for the formation of the myelin sheath in the human brain. In solution MBP is largely disordered and is considered as a prime example of an intrinsically disordered protein (IDP). Using X-ray and neutron scattering techniques (SAXS/SANS as well as QENS and NSE) we investigated the structural and dynamic properties of MBP in solution and the inherent differences of IDPs as compared to ideal polymers.

In further work, we extended our studies of biomimetic myelin systems. Previous studies observed that changes in the myelin lipid composition during multiple-sclerosis (MS) conditions lead to instabilities and enhanced local curvature of MBP-lipid multilayer structures. We investigated the molecular origin of the instability using a combination of neutron and X-ray scattering techniques as well as cryo-transmission electron microscopy. We found that the MS lipid membrane has a 25% lower bending rigidity than the native one, thus destabilizing smooth > 1 μm curvature radius structures such as in giant unilamellar vesicles. MBP-mediated assembling of lipid bilayers proceeds in two steps, with a slow second step occurring over many days where native lipid membranes assemble into well-defined multilayer structures, whereas MS diseased lipid membranes form folded assemblies with high local curvature. For both native and diseased lipid mixtures we could show that MBP forms concentrated liquid-like phases on top of the lipid membranes mediating attractive membrane interactions. In recent work, we could demonstrate that MBP performs a liquid-liquid phase separation (LLPS) under crowding conditions in vitro. Time-resolved small-angle neutron and X-ray scattering as well as dynamic light scattering experiments allowed us to follow the size evolution kinetics of LLPS condensates consisting of MBP for more than six orders of magnitude in time. Spinodal decomposition and subsequent Ostwald ripening appear to be main driving forces for LLPS droplet formation of MBP in vitro.

Bio: Andreas studied physics and biophysics at Technical University Munich, Germany, and at University Pierre and Marie Curie, Paris, France. He obtained his PhD degree with Dr. Giuseppe Zaccai in 2009 in physics in the field of protein dynamics using quasielastic incoherent neutron spectroscopy as experimental method. After that he joined Forschungszentrum Julich to work first on a project using coherent X-ray diffraction in molecular biophysics, and later joined JCNS in 2011 to start working on the structure and dynamics of intrinsically disordered proteins using small-angle neutron and X-ray scattering and neutron spin-echo spectroscopy. Since 2015 he is senior scientist with permanent position and in 2019 he obtained his habilitation from RWTH Aachen University in chemistry.

His current research interests are focused on the investigation of the structure and dynamics of intrinsically disordered proteins and on the relevance of molecular flexibility for biological function. Experimental techniques used include neutron spectroscopy and small-angle X-ray and neutron scattering.

In May–June 2023, Andreas Stadler is a Guest Researcher at LINXS within the IPDD theme.

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