title: Beyond the hydrophobic effect: Critical function of water at biological phase boundaries--A hypothesis.
abstract: 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.
authors.affiliation: University of Wisconsin-Madison, Department of Food Science, 1605 Linden Drive, Madison, WI 53706, United States. Electronic address: sdamodar@facstaff.wisc.edu.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Damodaran
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D055119:Elastic Modulus / Q000502:physiology; D004926:Escherichia coli / Q000737:chemistry / Q000502:physiology; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008560:Membrane Fluidity / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D013314:Stress, Mechanical; D014867:Water / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D014867:Water
keywords: G-protein activation; Interfacial activation of enzymes; Interfacial water activity; Mechanoactivation; Membrane function