Protein-lipid interactions and membrane remodeling
Our research in membrane biophysics aims to understand how proteins and lipids conspire to determine the shape and organization of biological membranes, in order to improve our ability to manipulate these systems for medical and biotechnical applications. More specifically, we are interested in mechanisms for sensing and generation of membrane curvature by proteins and small molecules.
These questions are difficult to study experimentally, because of the limited resolution of light microscopy, while more accurate methods such as NMR are difficult to apply to curved membrane systems. Computer simulations are therefore an important complement. Our previous efforts have focused on membrane deformation induced by the monotopic protein MGS, a model system for regulation of mechanical properties of membranes (1), and on developing new computational methods for studying curvature sensing (manuscripts in preparation).
Our new method is based on simulated membrane buckling, and requires long simulations of larger membrane patches than normally used to study single membrane proteins, typically ~1000 lipids for tens of microseconds. This is only feasible with coarse-grained models, in our case the widely popular Martini force field. The idea to use buckled membranes to study curvature sensing computationally has not been tried in a systematic way.
Our model systems are of broad biophysical interest. Mechanisms that organize and shape cell membranes are of fundamental importance in cell biology and medicine, and a quantitative understanding of membrane shaping mechanisms may be useful for the design of soft matter devices.
Our ongoing activity concerns membrane curvature sensing by cardiolipin and by amphiphatic helices. Cardiolipin is a bacterial lipid with unusual shape, which is involved in polar localization of both lipids and proteins and critical for the functioning of mitochondria. Amphiphatic are universal sensor motifs of membane curvature, and a common motif for antimicrobial peptides. During the coming year, we plan to apply our new methods to study curvature sensing by the proton channel M2, a small transmembrane protein involved in the budding process of influenza viruses. We also plan further method development, in particular to speed up the computations using enhanced sampling methods such as meta-dynamics.
1. Ge, C., J. Gómez Llobregat, M. Skwark, Jean-Marie Ruysschaert, Wieslander, Åke, and M. Lindén (2014). Membrane Remodeling Capacity of a Vesicle-inducing Glycosyltransferase. FEBS J. (in press).
The PI has recently moved to Uppsala University, but this application concerns a project that is still situated at the old affiliation, the Dept. of Biochemistry and Biophysics at Stockholm University.