Prof. Sandro Keller "Solubilization of Membrane Proteins into Functional Lipid-Bilayer Nanodiscs Using Amphiphilic"

Detergents are traditionally used for extracting and solubilising membrane proteins. In the highly dynamic environment of a detergent micelle, however, many membrane proteins tend to denature irreversibly. Some styrene/maleic acid (SMA) copolymers enable a funda-mentally new approach for investigating membrane proteins, as they obviate the use of conventional, harsh detergents. These polymers can extract proteins and surrounding lipids directly from cellular membranes to form nanosized discs, where the polymer wraps around a lipid-bilayer patch. Such nanodiscs are readily amenable to optical and nuclear magnetic resonance (NMR) spectroscopy, which sets them apart from traditional bilayer systems such as vesicles. We combine these spectroscopic methods with concepts from solution thermodynamics to rationalise polymer/lipid interactions and thus fully exploit the potential of SMA for membrane-protein research (Vargas et al. Nanoscale 2015, 7, 20685; Cuevas Arenas et al. Nanoscale 2016, 8, 15016; Cuevas Arenas et al. Sci. Rep. 2017, 7, 45875).

In this talk, I will show that another copolymer named diisobutylene/maleic acid (DIBMA) is equally capable of accommodating membrane proteins and lipids in native nanodiscs, thus rendering them amenable to physicochemical scrutiny. The major advantage of this new polymer lies in the fact that it is compatible with optical spectroscopy in the ultraviolet range, does not disturb the order, dynamics, and hydration of the solubilised membrane fragment, and tolerates elevated concentrations of metal ions often required for protein activity (Oluwole et al. Angew. Chem. Int. Ed. 2017, 56, 1919; Grethen et al. Sci. Rep. 2017, accepted).

invited by Prof. Winfried Römer & Taras Sych