Beyond the hydrophobic effect: Critical function of water at biological phase boundaries — A hypothesis

• Surface pressure is a measure of interfacial water activity.
• Surface pressure-dependent biological processes are inherently controlled by interfacial water activity.
• Receptor-activator systems in biomembranes function as devices to manipulate local interfacial water activity.
• Mechanosensitive signaling processes are fundamentally related to changes in thermodynamic state of interfacial water.

Many life-sustaining processes in living cells occur at the membrane–water interface. The pertinent questions that need to be asked are what is the evolutionary reason for biology to choose the membrane–water interface as the site for performing and/or controlling crucial biological reactions and what is the key physical principle that is singular to the membrane–water interface that biology exploits for regulating metabolic processes in cells? In this review, a hypothesis is developed, which espouses that cells control activities of membrane-bound enzymes and receptor activated processes via manipulating the thermodynamic activity of water at the membrane–water interfacial region. In support of this hypothesis, first we establish that the surface pressure of a lipid monolayer is a direct measure of a reduction in the thermodynamic activity of interfacial water. Second, we show that the surface pressure-dependent activation/inactivation of interfacial enzymes is fundamentally related to their dependence on interfacial water activity. We extend this argument to infer that cells might manipulate activities of membrane-associated biological processes via manipulating the activity of interfacial water via localized compression or expansion of the interface. In this paper, we critically analyze literature data on mechano-activation of large pore ion channels in Escherichia coli spheroplasts and G-proteins in reconstituted lipid vesicles, and show that these pressure-induced activation processes are fundamentally and quantitatively related to changes in the thermodynamic state of interfacial water, caused by mechanical stretching of the bilayer.

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