8 December 2023
Songi Han
Department of Chemistry
Northwestern University
The ability to "turn the lights on" to directly see the molecular machinery of life fundamentally changes how we understand and manipulate biology. One such material that is so fundamental to how the molecular machinery of life operates, in what way molecules interact, associate, assemble and perform chemical and biological processes, but is exceptionally difficult to characterize is water. Water has properties of a molecule and a material, it is a liquid with fluid properties, but it also has structure, and in fact adopts multiple structures in solutions containing your favorite protein. After all, is there such thing as structured water in liquid water? Yes, there is! I will briefly go over 3-4 key nuclear magnetic resonance and electron-nuclear double resonance spectroscopy tools of 1H and 17O to identify the dynamical, structural, and thermodynamical property of water that varies with the surface chemistry and topology of the dissolved small molecules or biological macromolecules. Some of them are old tricks but re-invented, some are new tricks, and some are well known tools. I will also talk about some of the critical control experiments that you will need to hear about to believe the rest of my story. But I will start my discussion from a different angle so that we don’t forget in this discussion why does it matter whether shaping of water exist or not and can be measured. I will ask you to think about what criteria do molecules have to fulfill to be a "prion", the protein assembly state that adopts a misfolded protein shape and can recruit naïve proteins to be infected and assimilated to take on same shape and perpetuate this pattern in way that wreaks havoc in the infected person. Figuring this out might be at the crux of finding at least a diagnostic tool or, even better, a therapeutic strategy for Alzheimer’s disease and other tauopathies. I will also ask you to think about to imagine the perfect antifreeze molecule or material. What do you think such an agent has to accomplish to prevent ice from growing and propagating? When you are asked these questions without being an expert in the protein aggregation or neurodegenerative disease community or the antifreeze community, I would not be surprised if you landed at the same answer and hypotheses as I did. In that sense, I am thinking that my hypothesis and proposal are not extraordinary, just logical. Yet, the two hypotheses that I will present that guides our currently ongoing studies for these two questions are considered out of line, opposite to many existing design criteria or fringe or "cute" ideas that not many people think are that relevant to solving the problem. The solution to this dilemma is that we simply must go all the way to demonstrating the viability of our hypotheses and potentially making first steps towards finding solutions to generating disease-specific aggregate strain (currently rarely accomplished, at least not rationally) or antifreeze agents (which is so complex that experts explain that this is "black art"). Once it’s clear why we need to empirically measure the shape of water, I hope I will be able to briefly tell you about the principles behind the measurements, and why it was not done or not routinely done by others. Time permitting, I will discuss some of the control experiments we did with DMSO, glycerol or phosphate anions that you might find equally fascinating as the complex systems, especially because I should be able to tell you something about these "simple" mixtures that are not so simple.