Use the Force, Luke!

A couple nice force spectroscopy papers this week. The first comes out of our lab, by Matt Larson, studying the mechanism by which RNA hairpins cause termination in RNA polymerase. The common theory is that the U-rich RNA in the active site forms a "greasy" tract which is easily yanked out by the forming RNA hairpin. Matt finds evidence supporting this hypothesis, but finds that the mechanics of similar hairpin terminators (t500 and tR2, for instance) effect termination in mechanistically different fashions, which is quite surprising. The paper is worth a read, if for no other reason than to understand the real power of using single molecule force experiments to study mechanisms which are difficult to probe using traditional biochemical approaches.

There's also an interesting looking review in ChemPhysChem (what a bad name for a journal, by the way) looking at the use of AFM to learn about the structure of membrane proteins by yanking them out of the membrane. I think that finding ways to apply force spectroscopy to membrane proteins is going to be huge, but I think that just yanking them out of the membrane, while interesting from an energetics standpoint, is kind of crude. It's a tough problem, though, to figure out how to apply forces to membrane proteins without yanking them out of the membrane. Some of my graduate work was on ion channels, so I have some familiarity with the field, and I've spent some hours dreaming about it, but it's a tough nut to crack. Essentially, you want to be able to cleanly attach handles to membrane-bound objects in an in vitro setting, in such a way that you can still modulate them (by voltage, ligand, or mechanical strain, for instance) and then use your handle to probe and apply forces without pulling the whole thing out of the membrane. I've dreamed of using unilammelar vesicles, or lipid bilayers painted onto electrode patterned coverslips, but the complexity seems overwhelming. I'm still dreaming, though.

Also, taking the "Use the Force" metaphor a different direction, a shout out to my homey Greg Snyder who writes in to say, "I know this isn't single-molecule biophysics, but it is cool optics." White holes, black holes, fiber optics...next thing you know we'll be writing about Transdimensional Monte Carlo Hyperdrives.