Tuesday, January 23, 2007

Mostly hydrophobic

With a daunting glut of papers this week, I can do little more than list them. Daniel Blankschtein and colleagues at MIT have a series of three papers the aim to quantify the hydrophobic effect responsible for aggregation of amphiphiles in solution. At issue here is the question of how changes in hydration of the different parts of amphiphile molecules on aggregation into structures such as micelles (but also, of course, bilayer membranes) provide a driving force for the self-assembly process. Blankschtein and colleagues explore this through computer simulation. The three articles look respectively at aggregation of oils, non-ionic surfactants, and ionic/zwitterionic surfactants. The general aim is to be able to model and predict the changes in hydration, and the consequent hydrophobic driving force for aggregation, sufficiently to be able to predict bulk parameters such as the critical micelle concentration. The work is, as far as I can see, at this stage concerned with developing and validating the methodology; presumably it could at some stage be used to look at the more complex structures formed by lipids, and perhaps at protein aggregation and self-assembly too.

That's in a sense also the topic of a paper in Biochemistry by Ronald McElhaney of the University of Alberta and colleagues, which asks how hydrophobic an alpha-helical peptide needs to be in order to get inserted stably into a phospholipid bilayer. Specifically, they have looked at Leu-Ala sequences, where it seems that Leu/Ala ratios of more than 7/17 are needed in the helices for a stable transmembrane association. OK, so that's just a number, though presumably the kind of thing one needs to know in some areas of protein design. It also helps, perhaps unsurprisingly, to put the hydrophobic residues together on one side of the helix.

These questions of hydrophobic hydration are often examined by looking at small model hydrophobes. Benzene is a classic example, though it's not exactly a simple hydrophobe – it's been clear for some time that water molecules can hydrogen-bond to the pi-ring system. Markus Allesch at the Graz University of Technology and colleagues have studied the hydration of benzene, and also of hexafluorobenzene, in some detail using first-principles calculations. They find that both molecules act as hydrophobes equatorially, but that the pi-water interactions are quite subtle in the axial regions. A water molecule typically points towards the ring hydrogen-first for benzene, but lone-pair first for hexafluorobenzene. So one clearly shouldn't generalize even about something as seemingly simple as phenyl-group hydration.

I remember Jacob Israelachvili and Hakan Wennerström ruffling some feathers with their review article in Nature on the hydration of hydrophilic surfaces. It was controversial then, and it still is now. One of the issues is why phospholipids bilayers repel one another at short ranges. Alexander Pertsin of the University of Heidelberg and his colleagues have explored the matter in a paper in Langmuir using Monte Carlo simulation. They point out that there are two leading theories: the repulsion is either entropically driven (confinement by proximity of the bilayers suppresses fluctuations and so decreases entropy), or it arises from a perturbation of water structure in the intervening film. (Israelachvili and Wennerström were dismissive of 'water structuring' theories). There are, for example, suggestions that orientation of the interfacial water plays a role. I'm still chewing on this paper, but it clearly supports the view that the repulsion arises from hydration changes rather than entropic effects or protruding lipid headgroups. I've got a feeling this isn't going to be the last word on the matter.

Finally – well, not quite, but for now – Barry Ninham and his collaborators in Italy have been probing the puzzles of the Hofmeister effect: ion-specific effects of electrolytes on proteins. The classic effect identified by Hofmeister himself was on protein precipitation, but there's plenty else to this phenomenon. In one study, Barry and co. find that different sodium salts have markedly different effects on the enzymatic activity of a lipase: NaSCN can inactivate it completely, while sodium sulphate activates it and sodium chloride has little effect at all. What's going on? The researchers eschew generalized and, I think, questionable ideas about whether particular ions 'make' or 'break' water structure (that is, whether they are kosmotropes or chaotropes), and focus instead on how the specific ions might interact with the protein and its hydration shells. The devil is in the details.

A second paper looks at Hofmeister effects in phospholipids aggregation. Again, the issue is exactly how the ions interact with the organic molecules and their hydration shells: in this case, how they affect hydration and packing of lipid headgroups in micellar aggregates. That, it seems, may depend in this case on the anionic polarizabilities. It all gives me some faith that structure-making and structure-breaking is a concept on the way out – though the alternative will be messy, and it's not yet clear that it will yield handy generalizations.

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