Understanding and Controlling Defects and their Impact on Function, Structure and Activity in Lipid Membranes
Project areas:
Biophysics
Organic Molecular Chemistry - Synthesis and Characterization
Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
Project leaders:
Schneider, Dirk, Prof. Dr.
Johannes Gutenberg University Mainz
Department of Chemistry
Hanns-Dieter-Hüsch-Weg 17, 55128 Mainz
+49 6131 39-25833
dirk.schneider[a]uni-mainz.de
Wahl, Johannes M., Prof. Dr.
Johannes Gutenberg University Mainz
Department of Chemistry
Duesbergweg 10–14, 55128 Mainz
+49 6131 39-23242
wahl[a]uni-mainz.de
Summary
At first glance, biological membranes that constitute cytoplasmic membranes and separate organelles from
the surrounding cytoplasm, seem to be simple and passive barriers. A closer look reveals that membranes are composed of a plethora of different lipid species and contain integral or peripherally attached proteins.
Although mixtures of the basic membrane building blocks, the membrane lipids (mainly phospholipids),
predominantly form a disordered two-dimensional liquid, complex phenomena such as ordering, local lipid de-mixing, lipid domain formation, and formation of non-canonical membrane structures can occur. Yet, even
subtle spatio-temporal changes in the membrane structure can have a dramatic influence on the
transmembrane permeation of ions and small molecules or the spatial arrangement and the activity of
membrane proteins. Furthermore, several proteins recognize, and potentially even extend defects in the
membrane structure. Thus, the membrane organization is crucial for structuring, organizing and regulating the functionality of proteins, organelles and whole cells. Many of these complex intramembranous interactions are still not understood. It is e.g. still unclear, how a disruption in the membrane’s continuity, such as a change in structure (lipid domains), local exposure of hydrophobic regions, a change in curvature or a membrane-incorporated protein influences the local structuring and composition in the vicinity of the defect. In this project, we will investigate the “behavior” of a membrane in the vicinity of a membrane defect, which has been generated using different triggers. Membrane defects will be introduced in a controlled way using i) small molecules, ii) lipid modifying enzymes and iii) membrane-binding proteins. Furthermore, (iv) we will develop novel photoswitchable phospholipid systems that can be incorporated into model membranes. Thereby, we will be able to activate and de-active membrane defects during an experiment. Particularly interesting are photoswitchable systems that do not only rely on geometrical changes to disturb the ideal membrane structure, but also feature polarity and reactivity alterations. Through the development of a new “chemistry within a membrane” and installation of novel photochemical response groups, different types of defects will be initiated and their overall effect on the membrane structure, function and stability analyzed. We will use synthetic, biochemical and biophysical methods such as atomic force microscopy (AFM) to study the generation, propagation and consequences of induced membrane defects. Here, we will study the local membrane topology as well as local changes in structure and composition around membrane defects directly in a liquid environment.