Solid-State NMR of Biomolecules

How do large molecules go through the membrane? How can we get a spectrum of a solid as informative as that of a solution? How to reconstruct the structure of polypeptides knowing the orientation of molecules? These and other questions are answered by head of NMR and membrane biophysics team of the CNRS and University of Strasbourg, Burkhard Bechinger.

In our team we are interested in applying biophysical methods to membrane proteins and membrane peptides. This has very important implications in many biomedical research areas like the field of antimicrobic peptides, but also how the signalling occurs through the membrane, how can molecules be transported through the membrane, especially large molecules like DNA. That’s, for example, gene therapy – we want to transport the DNA into the cells where you have to past the membrane. Or there are other signals that past the membrane to have contact from the inside to the outside of the cell. And all of this happens or a lot of these things happen with membranes, with proteins that are situated in the membranes, or peptides. And so we want to study the structure of these more.

There are many biophysical techniques like optical spectroscopy, CD, infrared, where you can get secondary structure, but one technique that is very powerful is solid-state NMR spectroscopy. So now probably you have heard about NMR spectroscopy a lot and you learned it in your courses and so on. It’s a very popular technique nowadays, because it’s so potent and has so many applications. But most people apply NMR in the liquid state. And what happens is the molecule stumbles very fast and that many interactions get averaged during time, because the molecules move so fast. That’s good, because it gives you for one atom – one signal, and it’s a sharp signal. And if the systems get bigger and bigger, the peaks get broader and broader, so there’s a limit for that. That’s when there, at that point, solid state NMR steps in, because that’s the technique that has been developed for systems that are actually not moving, that are solid. And it’s also NMR, but now things get more complicated.

Why hasn’t solid state NMR been developed parallel to solution NMR? – you may ask. Well, one problem is that the lines are so broad we didn’t get the resolution that you automatically get in solutions, but not automatically in the solids. So you have to take artificial means to get narrow lines, for example. And we also need much more samples, and it’s sometimes difficult for biomicromolecules to have so much samples. So these are the disadvantages. So I think the field will actually profit from novel technical developments. And these developments are, for example, some signal enhancement techniques that can be through pulse sequence, through bigger magnets, but also through what we call dynamic nuclear polarization, where we transfer polarization from electrones to the nuclei and make them much more intense that way. There might be new things coming up, which we don’t even think about. But this is sort of a major hurdle.