The NMR 'split peak effect' in cell suspensions: Historical perspective, explanation and applications.

The physicochemical environment inside cells is distinctly different from that immediately outside. The selective exchange of ions, water and other molecules across the cell membrane, mediated by integral, membrane-embedded proteins is a hallmark of living systems. There are various methodologies available to measure the selectivity and rates (kinetics) of such exchange processes, including several that take advantage of the non-invasive nature of NMR spectroscopy. A number of solutes, including particular inorganic ions, show distinctive NMR behaviour, in which separate resonances arise from the intra- and extracellular solute populations, without the addition of shift reagents, differences in pH, or selective binding partners. This 'split peak effect/phenomenon', discovered in 1984, has become a valuable tool, used in many NMR studies of cellular behaviour and function. The explanation for the phenomenon, based on the differential hydrogen bonding of the reporter solutes to water, and the various ways in which this phenomenon has been used to investigate aspects of cellular biochemistry and physiology, are the topics of this review.