CLASSES OF HYDRATION SITES AT PROTEIN-WATER INTERFACES - THE SOURCE OF CONTRAST IN MAGNETIC-RESONANCE-IMAGING

Immobilized protein solute, similar to 20 wt%, alters the longitudinal and transverse nuclear magnetic relaxation rates 1/T-1 and 1/T-2 of s olvent water protons in a manner that makes their values indistinguish able from those of a typical human tissue. There is now a quantitative theory at the molecular level (S. H. Koenig and R. D. Brown III (1993 ) Magn. Reson. Med. 30:685-695) that accounts for this, as a function of magnetic field strength, in terms of several distinguishable classe s of water-binding sites at the protein-water interface at which signi ficant relaxation and solute-solvent transfer of proton Zeeman energy occur. We review the arguments that these several classes of sites, ch aracterized by widely disparate values of the resident lifetimes tau(M ) of the bound waters, are associated with different numbers of hydrog en bonds that stabilize the particular protein-water complex. The site s that dominate relaxation-and produce contrast in magnetic resonance imaging (MRI), which derives from 1/T-1 and 1/T-2 of tissue water prot ons-have tau(M) approximate to 10(-6) s. These, which involve four hyd rogen bonds, occupy less than or equal to 1% of the protein-water inte rface. Sites that involve three bonds, although more numerous, have le ss than or equal to 20% smaller intrinsic effect on relaxation. The gr eater part of the ''traditional'' hydration monolayer, with even short er-lived hydrogen-bonded waters, has little influence on solvent relax ation and is relatively unimportant in MRI. Finally, we argue, from th e data, that most of the protein of tissue (a typical tissue is mostly protein) must be rotationally immobile (with Brownian rotational rela xation times slower than that of a 5 x 10(7) Da (very heavy) globular protein). We propose a functional basis for this immobilization (''cyt oplasmic order''), and then indicate a way in which this order can bre ak down (''cytoplasmic chaos'') as a result of neoplastic transformati on (cancer) and alter water-proton relaxation rates of pathological ti ssue and, hence, image contrast in MRI.