Figure 4. This diagram shows the clustering around two K+-carboxylate ion pairs (about 4 nm apart) as may be attached to part of two protein’s structures. There are 7-8 shells of water around each surface as is typically found between intracellular proteins. The K+ ions are shown as violet and the water network is shown as linked (i.e. hydrogen bonded) oxygen atoms (shown red) without showing their associated hydrogen atoms. The hydrogen bonding initially forms clathrate cages around the ion pairs, followed by a more extensive icosahedral arrangement. This is then followed by extension of the hydrogen bonding along ‘rays’ connecting the neighbouring sites. Once these ‘rays’ link, the hydrogen bonding of each reinforces the other in a cooperative manner, so strengthening the linkage and reinforcing the overall low density aqueous environment. As the aqueous clathrate cage possesses a more negative charge on its interior and a more positive charge on the outside, there is a marked polarization in the water molecules that reinforces the hydrogen bonding interactions.

Although the clustering involves a major drop in aqueous mobility, the stronger 4-coordinated bonding compensates this. This theory offers a molecular explanation for Ling’s association-induction polarized multilayer model (see “Strong medicine needed in cell biology”, this issue). The initial icosahedral size (3 nm diameter), surrounding each ion pair, also equals the water domain size proposed by John Watterson. The tetrahedral structuring possesses five-fold symmetry, which prevents easy freezing in line with the pronounced supercooling found for intracellular water.

Extension of the clathrate network and its associated low density water enables K+ ion binding to all aspartic and glutamic acid groups, not just the key ones within the crucial N-terminal acidic centres. Thus, the sol-gel transition of Pollack (see “Biology of least action”, SiS 18) may be interpreted as due to the formation of low density water clustering (the gel state) due to clathrate clustering around K+-carboxylate ion pairs.

In the presence of raised levels of Na+ and/or Ca2+ ions, as occasionally occurs during some cell functions, these ions will replace some of the bound K+ ions. These newly formed solvent separated Na+ and/or Ca2+ ion pairings destroy the low-density clathrate structures and initiate a cooperative conversion of the associated water towards a denser structuring.
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