Membrane Biophysics

Membrane protein structure and function are coupled to the structure and composition of their membrane environment. The characterization of this interplay between the membrane and embedded proteins is experimentally challenging. A variety of solid-state NMR experiments provide unique structural as well as motional insight into not only the protein, but also the lipids. In the Van der Wel group we use various types of ssNMR spectroscopy for the characterization of the biophysics of protein-lipid interactions, in which also the study of lipid dynamics and structure is an important focal point. Such studies are critical for understanding (peripherally) membrane-associated proteins, the functioning of antimicrobials, toxic effects in amyloid diseases and many much more. Through static SSNMR as well as magic angle spinning NMR, we investigate the membrane and its response to proteins or peptides. This has yielded insights into e.g. protein-induced membrane disruption [1], ordering and disordering of membranes due to cholesterol and protein incorporation [2], and the features of structurally valuable 2D crystals of membrane proteins [3]. Also see here.

Selected References

  1. Van der Wel, P.C.A. et al. (2000) Tryptophan-anchored transmembrane peptides promote formation of nonlamellar phases in phosphatidylethanolamine model membranes in a mismatch-dependent manner. Biochemistry 39: 3124-33. *
  2. Hoop, C.L., Sivanandam, V.N., Kodali, R., Srnec, M.N., Van der Wel, P.C.A. (2012) “Structural Characterization Of The Caveolin Scaffolding Domain In  Association With Cholesterol-Rich Membranes.” Biochemistry, 51(1): 90-99 [doi]
  3. Eddy, M.T, Ong, T-C., Clark, L., Teijido, O., Van der Wel, P.C.A., Garces, R., Wagner, G., Rostovtseva, T.K., and Griffin, R.G. (2012) Lipid Dynamics and Protein-Lipid Interactions in 2D Crystals Formed with the β-barrel Integral Membrane Protein VDAC1.  J. Am. Chem. Soc., 134(14): 6375-6387 [doi]
  4. Mandal, A. et al. (2015) Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Biophys. J. 109(9): 1873–1884 [doi]
  5. Mandal and Van der Wel (2016) MAS 1H NMR Probes Freezing Point Depression of Water and Liquid-Gel Phase Transitions in Liposomes. Biophys. J. 111(9): 1965-1973 [doi]