Georg Pabst

Applications of neutron and X-ray scattering to the study of biologically relevant model membranes

Scattering techniques, in particular electron, neutron and X-ray scattering have played a major role in elucidating the static and dynamic structure of biologically relevant membranes. Importantly, neutron and X-ray scattering have evolved to address new sample preparations that better mimic biological membranes. In this review, we will report on some of the latest model membrane results, and the neutron and X-ray techniques that were used to obtain them.

GLOBAL PROPERTIES OF BIOMIMETIC MEMBRANES: PERSPECTIVES ON MOLECULAR FEATURES

Global properties of biological model membranes such as, e.g., structure or elasticity, are known to be closely related to their local features. If a membrane active compound interacts with the membrane assembly, the membrane will primarily be affected on the local, molecular level. The local perturbation may than, through some coupling, translate into a global adjustment of the membrane. In order to address this coupling x-ray and neutron diffraction data analysis techniques have been developed that allow accurate monitoring of changes in global properties. This offers new perspectives on molecular membrane features that in combination with complementary techniques, such as differential scanning calorimetry, spectroscopy or dynamic scattering lead to a better understanding of biomimetic membranes. The present article reviews these aspects giving application examples for single- and multicomponent membranes, respectively.

Asymmetric Lipid Membranes: Towards More Realistic Model Systems

Despite the ubiquity of transbilayer asymmetry in natural cell membranes, the vast majority of existing research has utilized chemically well-defined symmetric liposomes, where the inner and outer bilayer leaflets have the same composition. Here, we review various aspects of asymmetry in nature and in model systems in anticipation for the next phase of model membrane studies.

Coupling Membrane Elasticity and Structure to Protein Function

Abstract Elasticity is one of the crucial parameters for the functioning of biological membranes. This chapter focuses on the coupling of lipid membrane properties, such as spontaneous curvature, bending rigidity, and Gaussian modulus of curvature to ion-channel activity. For this purpose, current theories of coupling mechanisms, such as the lateral pressure concept and hydrophobic matching, are reviewed and discussed. A brief tutorial on the experimental determination of membrane elastic parameters is presented, focusing mainly on X-ray scattering in combination with osmotic stress. Finally, the theory is applied on funnel-shaped and hourglass-shaped ion channels in the context of enzymatic hydrolysis of sphingomyelin, using experimental data.

Complex biomembrane mimetics on the sub-nanometer scale

Biomimetic lipid vesicles are indispensable tools for gaining insight into the biophysics of cell physiology on the molecular level. The level of complexity of these model systems has steadily increased, and now spans from domain-forming lipid mixtures to asymmetric lipid bilayers. Here, we review recent progress in the development and application of elastic neutron and X-ray scattering techniques for studying these systems in situ and under physiologically relevant conditions on the nanometer to sub-nanometer length scales. In particular, we focus on: (1) structural details of coexisting liquid-ordered and liquid-disordered domains, including their thickness and lipid packing mismatch as a function of a size transition from nanoscopic to macroscopic domains; (2) membrane-mediated protein partitioning into lipid domains; (3) the role of the aqueous medium in tuning interactions between membranes and domains; and (4) leaflet-specific structure in asymmetric bilayers and passive lipid flip-flop.

Scattering techniques in biology--Marking the contributions to the field from Peter Laggner on the occasion of his 68th birthday.

This special issue of the European Biophysics Journal marks the contributions of Peter Laggner to molecular biophysics and X-ray and neutron scattering techniques on the occasion of his 68th birthday. Actually, Peter Laggner is not a person who likes to dwell in the past, or talk of the good old days. ‘‘Why look back, if one can look forward?’’, is one of his most popular quotes. Well, we hope that he will forgive us on this one occasion. So, let us look back and recall some of the past from a rich life with many things to remember, but, to make it bearable, we will use an element of humor. Born in Piberbach, Upper Austria, Peter went to Graz to study chemistry and physics. During his PhD, he started with his so successful combination of small-angle X-ray scattering (SAXS), which he learned from the Austrian pioneer in SAXS, Otto Krakty, and biophysics, taught to him by Anton Holasek, then head of the Medical Biochemistry Institute, University of Graz. For his thesis on ‘‘Structure of Antigen Antibody Complexes in Solution by SAXS’’ Peter had an urgent need for blood. Therefore, this part of his career truly was bloody. Using his own car he would go to the slaughterhouse to fetch swine blood in buckets and then drive back to his laboratory. Occasionally blood spilled over. Who cares? In the laboratory the tedious job of precipitation and centrifugation awaited him, accompanied by anxious moments when the rotor lifted and the centrifuge started to move around. By dawn his eyes were blood-shot, but the proteins were prepared and ‘‘real science’’ could start. Soon afterwards lipoproteins—high-density (HDL) and low-density lipoproteins (LDL)—caught Peter’s scientific interest. Again, blood had to be isolated, and trouble started from the beginning. This time the blood had to be of human origin. Thus, healthy normolipidemic volunteers were required. By chance, PhD students were ‘‘lucky’’ to act as donors for Peter’s blood pool, but the most fascinating thing was, however, to use one’s own blood, as he always told us. Later, lipoprotein subspecies came in from John Chapman in Paris, making life much easier. However, whenever whole blood was harvested in our laboratory, Peter was among the first to put his name on the list of donors, eager to support our common efforts to solve the structure of LDL. One day, early in the morning, Peter arrived at the laboratory with a bottle of warm blood in his hands and laughed, ‘‘Hey girls, I have been at the doctor and thought I could bring you some fresh blood!’’, remembers Ruth Prassl. Peter’s pioneering work on lipoproteins has significantly shaped our current understanding of lipoprotein structure and dynamics. In addition to his research focus on LDL, Peter devoted a large part of his endeavor towards understanding complex biological membranes. Early on, he considered the membrane as a dynamic entity with spatial and temporal fluctuations in its local composition. So, he initiated structural studies on lipid polymorphism and domain formation, long before the term ‘‘membrane rafts’’ became popular. A particularly important study concerns the demonstration of chain interdigitated bilayers in ether-chain lipid membranes. He also pioneered lipid interactions with membrane-active peptides, showing that melittin from bee venom acts on membrane collective properties at concentrations as low as 1/1,000 (peptide/lipid molar ratio). G. Pabst (&) R. Prassl H. Amenitsch M. Rappolt K. Lohner Institute of Biophysics and Nanosystems Research, 8042 Graz, Austria e-mail: georg.pabst@oeaw.ac.at