Membrane Biophysics

Membrane protein structure as well as 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. Indeed, characterization of the biophysics of this interaction, and the biophysical study of the lipid bilayer per se are of great interest to studies of membrane-associated receptors, the functioning of antimicrobials, toxic effects in amyloid diseases and many key biomedical questions.

Through the use of static oriented and non-oriented 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]