Water at Biological Phase Boundaries: Its Role in Interfacial Activation of Enzymes and Metabolic Pathways

  • Srinivasan DamodaranEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 71)


Many life-sustaining activities in living cells occur at the membrane-water interface. The pertinent questions that we need to ask are, what are the evolutionary reasons in biology for choosing the membrane-water interface as the site for performing and/or controlling crucial biological reactions, and what is the key physical principle that is very singular to the membrane-water interface that biology exploits for regulating metabolic processes in cells? In this chapter, a hypothesis is developed, which espouses that cells control activities of membrane-bound enzymes through manipulation of the thermodynamic activity of water in the lipid-water interfacial region. The hypothesis is based on the fact that the surface pressure of a lipid monolayer is a direct measure of the thermodynamic activity of water at the lipid-water interface. Accordingly, the surface pressure-dependent activation or inactivation of interfacial enzymes is directly related to changes in the thermodynamic activity of interfacial water. Extension of this argument suggests that cells may manipulate conformations (and activities) of membrane-bound enzymes by manipulating the (re)activity of interfacial water at various locations in the membrane by localized compression or expansion of the interface. In this respect, cells may use the membrane-bound hormone receptors, lipid phase transition, and local variations in membrane lipid composition as effectors of local compression and/or expansion of membrane, and thereby local water activity. Several experimental data in the literature will be reexamined in the light of this hypothesis.


Enzyme activation Interfacial water Oscillatory reactions Membrane bound receptors 


  1. Auge N, Andrieu N, Negresalvayre A, Thiers JC, Levade T, Salvayre R (1996) The sphingomyelin-ceramide signaling pathway is involved in oxidized low-density lipoprotein-induced cell proliferation. J Biol Chem 271:19251–19255CrossRefPubMedGoogle Scholar
  2. Bianco ID, Fidelio GD, Yu RK, Maggio B (1992) Concerted modulation by myelin basic-protein and sulfatide of the activity of phospholipase-a2 against phospholipid monolayers. Biochemistry 31:2636–2641CrossRefPubMedGoogle Scholar
  3. Brady L, Brzozowski AM, Derewenda ZS, Dodson E, Dodson G, Tolley S, Turkenburg JP, Christiansen L, Huge-Jensen B, Norskov L, Thim L, Menge U (1990) A serine protease triad forms the catalytic centre of a triacylglycerol lipase. Nature 343:767–770CrossRefPubMedGoogle Scholar
  4. Broadskaya EN, Eriksson JC, Laaksonen A, Rusanov AI (1996) Local structure and work of formation of water clusters studied by molecular dynamics simulations. J Colloid Interface Sci 180:86–97CrossRefGoogle Scholar
  5. Brockman HL, Law JH, Kezdy FJ (1973) Catalysis by adsorbed enzymes: the hydrolysis of tripropionin by pancreatic lipase adsorbed to siliconized glass. J Biol Chem 248:4965–4970PubMedGoogle Scholar
  6. Burack WR, Biltonen RL (1994) Lipid bilayer heterogeneities and modulation of phospholipase A2 activity. Chem Phys Lipids 73:209–222CrossRefPubMedGoogle Scholar
  7. Burack WR, Dibble AR, Allietta MM, Biltonen RL (1997) Changes in vesicle morphology induced by lateral phase separation modulate phospholipase A2 activity. Biochemistry 36:10551–10557CrossRefPubMedGoogle Scholar
  8. Cantor RS (1997a) The lateral pressure profile in membranes: a physical mechanism of general anesthesia. Biochemistry 36:2339–2344CrossRefPubMedGoogle Scholar
  9. Cantor RS (1997b) Lateral pressures in cell membranes: a mechanism for modulation of protein function. J Phys Chem B 101:1723–1725CrossRefGoogle Scholar
  10. Carriere F, Thirstrup K, Hjorth S, Ferrato F, Nielsen PF, Withers-Martinez C, Cambillau C, Boel E, Thim L, Verger R (1997) Pancreatic lipase structure-function relationships by domain exchange. Biochemistry 36:239–248CrossRefPubMedGoogle Scholar
  11. Cernia E, Battinelli L, Soro S (1996) Biocatalysed hydrolysis of triglycerides in emulsion and as monolayers. Thin Solid Films 284–285:727–730CrossRefGoogle Scholar
  12. Chang G, Spencer RH, Lee AT, Barclay MT, Rees DC (1998) Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science 282:2220–2226CrossRefPubMedGoogle Scholar
  13. Chen CS, Rosenwald AG, Pagano RE (1995) Ceramide as a modulator of endocytosis. J Biol Chem 270:13291–13297CrossRefPubMedGoogle Scholar
  14. Chiruvolu S, Zasadzinski AN (1993) Membrane elasticity effects on permeability measurements in vesicles. Am Inst Chem Eng J 39:647–652CrossRefGoogle Scholar
  15. Chmura SJ, Nodzenski E, Weichselbaum RR, Quintans J (1996) Protein kinase C inhibition induces apoptosis and ceramide production through activation of a neutral sphingomyelinase. Cancer Res 56:2711–2714PubMedGoogle Scholar
  16. Dahmen-Levison U, Brezesinski G, Moehwald H (1998) Enzymic hydrolysis of monolayers. A polarization modulated-infrared reflection absorption spectroscopy study. Prog Colloid Polym Sci 110:269–275CrossRefGoogle Scholar
  17. Damodaran S (1998) Water activity at interfaces and its role in regulation of interfacial enzymes: a hypothesis. Colloids Surf B Biointerfaces 11:231–237CrossRefGoogle Scholar
  18. Damodaran S, Song KB (1986) The role of solvent polarity in the free energy of transfer of amino acid side chains from water to organic solvents. J Biol Chem 261:7220–7222PubMedGoogle Scholar
  19. Davies JT (1956) A surface equation of state for charged monolayers. J Colloid Sci 11:377–390CrossRefGoogle Scholar
  20. Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiol Rev 75:519–560PubMedCentralPubMedGoogle Scholar
  21. Davies JT, Rideal EK (1963) Interfacial phenomena, 2nd edn. Academic, New YorkGoogle Scholar
  22. De Haas KH, Blom C, van den Ende D, Duits MHG, Mellema J (1997) Deformation of giant lipid bilayer vesicles in shear flow. Phys Rev E 56:7132–7137CrossRefGoogle Scholar
  23. Derewenda U, Brozozowski AM, Lawson DM, Derewenda ZS (1992) Catalysis at the interface – the anatomy of a conformational change in a triglyceride lipase. Biochemistry 31:1532–1541CrossRefPubMedGoogle Scholar
  24. Entressangies B, Desnuelle P (1974) Action of pancreatic lipase on monomeric tripropionin in the presence of water-miscible organic compounds. Biochim Biophys Acta 341:437–446CrossRefGoogle Scholar
  25. Fendri A, Sayari A, Gargouri Y (2004) Kinetic properties of turkey pancreatic lipase: a comparative study with emulsified tributyrin and monomolecular dicaprin. Chirality 17:57–62CrossRefGoogle Scholar
  26. Fowkes FM (1962) Ideal two-dimensional solutions. II. A new isotherm for soluble and gaseous monolayers. J Phys Chem 66:385–389CrossRefGoogle Scholar
  27. Gershfeld NL (1970) Intermolecular energies in condensed, lipid monolayers on water. J Colloid Interface Sci 32:167–172CrossRefPubMedGoogle Scholar
  28. Gomez-Fernandez JC, Aranda FJ, Villalain J, Micol V, Ortiz A, Hernandez T (1990) Modification by diacylglycerols of phospholipid vesicles structure and physical properties. Prog Clin Biol Res 343:53–58PubMedGoogle Scholar
  29. Gronberg L, Slotte JP (1990) Cholesterol oxidase catalyzed oxidation of cholesterol in mixed lipid monolayers: effects of surface pressure and phospholipid composition on catalytic activity. Biochemistry 29:3173–3178CrossRefPubMedGoogle Scholar
  30. Gudi S, Nolan JP, Frangos JA (1998) Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. Proc Natl Acad Sci U S A 95:2515–2519PubMedCentralCrossRefPubMedGoogle Scholar
  31. Hiemenz PC (1986) Principles of colloid and surface chemistry, 2nd edn. Marcel Dekker, New YorkGoogle Scholar
  32. Hirche F, Ulbrich-Hofman R (1999) The interfacial pressure is an important parameter for the rate of phospholipase D catalyzed reactions in emulsions systems. Biochim Biophys Acta 1436:383–389CrossRefPubMedGoogle Scholar
  33. Honger T, Jorgensen K, Stokes D, Biltonen RL, Mouritsen OG (1997) Phospholipase A2 activity and physical properties of lipid-bilayer substrates. Methods Enzymol 286:168–190CrossRefPubMedGoogle Scholar
  34. James SR, Paterson A, Harden TK, Demel RA, Downes CP (1997) Dependence of the activity of phospholipase Cβ on surface pressure and surface composition in phospholipid monolayers and its implications for their regulation. Biochemistry 36:848–855CrossRefPubMedGoogle Scholar
  35. Jungner M, Ohvo H, Slotte JP (1997) Interfacial regulation of bacterial sphingomyelinase activity. Biochim Biophys Acta 1344:230–240CrossRefPubMedGoogle Scholar
  36. Kapoor S, Werkmouller A, Goody RS, Waldmann H, Winter R (2013) Pressure modulation of ras-membrane interactions in intervesicle transfer. J Am Chem Soc 135:6149–6156CrossRefPubMedGoogle Scholar
  37. Koynova RD, Boyanov AL, Tenchov BG (1987) Gel state metastability and nature of the azeotropic points in mixtures of saturated phosphatidylcholines and fatty acids. Biochim Biophys Acta 903:186–196CrossRefGoogle Scholar
  38. Lio Y-C, Dennis EA (1998) Interfacial activation, lysophospholipase and transacylase activity of Group VI Ca2+-independent phospholipase A2. Biochim Biophys Acta 1392:320–332CrossRefPubMedGoogle Scholar
  39. Marguet F, Douchet I, Cavalier J-F, Buono G, Verger R (1999) Interfacial and/or molecular recognition by lipases of mixed monomolecular films of 1,2-dicaprin and chiral organophosphorus glyceride analogues? Colloids Surf B Biointerfaces 13:37–45CrossRefGoogle Scholar
  40. Martinac B, Buechner M, Delcour AH, Adler J, Kung C (1987) Pressure-sensitive ion channel in Escherichia coli. Proc Natl Acad Sci U S A 84:2297–2301PubMedCentralCrossRefPubMedGoogle Scholar
  41. Martinac B, Adler J, Kung C (1990) Mechanosensitive ion channels of E. coli activated by amphipaths. Nature 348:261–263CrossRefPubMedGoogle Scholar
  42. Middleton SR, Pallas NR, Mingins J, Pethica BA (2011) Thermodynamics of ionized monolayers: surface manometry on very low density spread monolayers of sodium octadecyl sulfate at the air/water interface and analysis of ionic double layer contributions to the isotherms. J Phys Chem 115:8056–8063Google Scholar
  43. Mingins J, Stigter D, Dill KA (1992) Phospholipid interactions in model membrane systems. 1. Experiments on monolayers. Biophys J 61:1603–1615PubMedCentralCrossRefPubMedGoogle Scholar
  44. Miyamoto S, Maeda T, Fujime S (1988) Change in membrane elastic modulus on activation of glucose transport system of brush border membrane vesicles studied by osmotic swelling and dynamic light scattering. Biophys J 53:505–512PubMedCentralCrossRefPubMedGoogle Scholar
  45. Moreau H, Pieroni G, Jolivet-Reynaud C, Alouf JR, Verger R (1988) A new kinetic approach for studying phospholipase C (Clostridium perfringens α toxin) activity on phospholipid monolayers. Biochemistry 27:2319–2323CrossRefPubMedGoogle Scholar
  46. Muderhwa JM, Brockman HL (1990) Binding of pancreatic carboxylester lipase to mixed lipid films: implications for surface organization. J Biol Chem 265:19644–19651PubMedGoogle Scholar
  47. Muderhwa JM, Brockman HL (1992) Lateral lipid distribution is a major regulator of lipase activity: implications for lipid-mediated signal transduction. J Biol Chem 267:24184–24192PubMedGoogle Scholar
  48. Myers D (1991) Surfaces, interfaces, and colloids. VCH Publishers, New YorkGoogle Scholar
  49. Needham D, Nunn RS (1990) Elastic deformation and failure of lipid bilayer membranes containing cholesterol. Biophys J 58:997–1009PubMedCentralCrossRefPubMedGoogle Scholar
  50. Obeid LM, Hannun YA (1995) Ceramide – a stress signal and mediator of growth suppression and apoptosis. J Cell Biochem 58:191–198CrossRefPubMedGoogle Scholar
  51. Pallas NR, Pethica BA (2009) Intermolecular forces in lipid monolayers. Two-dimensional virial coefficients for pentadecanoic acid from micromanometry on spread monolayers at the air/water interface. Phys Chem Chem Phys 11:5028–5034CrossRefPubMedGoogle Scholar
  52. Pattus F, Slotboom AJ, de Hass GH (1979) Regulation of phospholipase A2 activity by the lipid-water interface: a monolayer approach. Biochemistry 18:2691–2697CrossRefPubMedGoogle Scholar
  53. Perillo M, Yu RK, Maggio B (1994) Modulation of the activity of Clostridium perfringens neuraminidase by the molecular organization of gangliosides in monolayers. Biochim Biophys Acta 1193:155–164CrossRefPubMedGoogle Scholar
  54. Perozo EP, Cortes DM, Sompornpisut P, Klode A, Martinac B (2002) Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418:942–948CrossRefPubMedGoogle Scholar
  55. Peters GH, Dahmen-Levison U, de Meijere K, Brezesinski G, Toxvaerd S, Mohwald H, Svendsen A, Kinnunen PKJ (2000) Influence of surface properties of mixed monolayers on lipolytic hydrolysis. Langmuir 16:2779–2788CrossRefGoogle Scholar
  56. Pogram LM, Record MT Jr (2007) Hofmeister salt effects on surface tension arise from partitioning of anions and cations between bulk water and the air-water interface. J Phys Chem 111:5411–5417CrossRefGoogle Scholar
  57. Prosser AJ, Frances EI (2001) Adsorption and surface tension of ionic surfactants at the air-water interface: review and evaluation of equilibrium models. Colloids Surf A 178:1–40CrossRefGoogle Scholar
  58. Ransac S, Ivanova M, Verger R, Panaiotov I (1997) Monolayer techniques for studying lipase kinetics. Methods Enzymol 286:263–292CrossRefGoogle Scholar
  59. Rao CS, Damodaran S (2004) Surface pressure dependence of phospholipase A2 activity in lipid monolayers is linked to interfacial water activity. Colloids Surf B Biointerfaces 34:197–204CrossRefPubMedGoogle Scholar
  60. Rao CS, Damodaran S (2005) Activation of sphingomyelinase in lipid monolayer is related to interfacial water activity > Evidence from two disparate systems. Colloids Surf B Biointerfaces 45:49–55CrossRefPubMedGoogle Scholar
  61. Rogalska E, Nury S, Douchet I, Verger R (1995) Lipase stereoselectivity and regioselectivity toward three isomers of dicaprin: a kinetic study by the monomolecular film technique. Chirality 7:505–515CrossRefGoogle Scholar
  62. Ross J, Richter PH (1984) Dissipation regulation in oscillatory reactions – application to glycolysis – commentary. Adv Chem Phys 55:169–170Google Scholar
  63. Roussel A, Yang Y, Ferrato F, Verger R, Cambillau C, Lowe M (1998) Structure and activity of rat pancreatic lipase-related protein-2. J Biol Chem 273:32121–32128CrossRefPubMedGoogle Scholar
  64. Rupley JA, Careri G (1991) Protein hydration and function. Adv Protein Chem 41:37–172CrossRefPubMedGoogle Scholar
  65. Rupley JA, Yang P-H, Tollin G (1980) Thermodynamic and related studies of water interacting with proteins. In: Rowland SP (ed) Water in polymers. American Chemical Society, Washington, DC, pp 111–132CrossRefGoogle Scholar
  66. Salah AB, Sayari A, Verger R, Gargouri Y (2001) Kinetic studies of Rhizopus oryzae lipase using monomolecular film technique. Biochimie 83:463–469CrossRefPubMedGoogle Scholar
  67. Sasaki T, Hazeki K, Hazeki O, Ul M, Katada T (1995) Permissive effect of ceramide on growth factor-induced cell-proliferation. Biochem J 311:829–834PubMedCentralCrossRefPubMedGoogle Scholar
  68. Schmid RD, Verger R (1998) Lipases: interfacial enzymes with attractive applications. Angew Chem Int Ed 37:1608–1633CrossRefGoogle Scholar
  69. Schrag JD, Yunge L, Wu S, Cygler M (1991) Ser-His-Glu forms the catalytic triad of lipase from Geotrichum candidum. Nature 351:761–764CrossRefPubMedGoogle Scholar
  70. Schreiber I, Hung YF, Ross J (1996) Categorization of some oscillatory enzymatic reactions. J Phys Chem 100:8556–8566CrossRefGoogle Scholar
  71. Scott DL, Otwinowski Z, Gelb MH, Sigle PB (1990) Crystal structure of bee-venom phospholipase A2 in a complex with a transition state analog. Science 250:1563–1566CrossRefPubMedGoogle Scholar
  72. Smaby JM, Muderhwa JM, Brockman HL (1994) Is lateral phase-separation required for fatty-acid to stimulate lipases in a phosphatidylcholine interface. Biochemistry 33:1915–1922CrossRefPubMedGoogle Scholar
  73. Souvignet C, Pelosin J-M, Daniel S, Chambaz EM (1991) Activation of protein kinase C in lipid monolayers. J Biol Chem 266:40–44PubMedGoogle Scholar
  74. Sukharev SI, Blount P, Martinac B, Blattner FR, Kung C (1994) A large-conductance mechanosensitive channel in E. coli encoded by mscL alone. Nature 368:265–268CrossRefPubMedGoogle Scholar
  75. Sukharev SI, Sigurdson WJ, Kung C, Sachs F (1999) Energetic and spatial parameters for gating of the bacterial large conductance mechanosensitive channel, MscL. J Gen Physiol 113:525–539PubMedCentralCrossRefPubMedGoogle Scholar
  76. Tanaka K, Manning PA, Yu H (2000) Lipase catalysis on monolayers at the air/water interface. 1. Kinetic rate constants on quasi-two-dimension. Langmuir 16:2665–2671CrossRefGoogle Scholar
  77. Thuren T, Wilcox RW, Sisson P, Waite M (1991) Hepatic lipase hydrolysis of lipid monolayers. J Biol Chem 266:4853–4861PubMedGoogle Scholar
  78. Tsujita T, Brockman HL (1987) Regulation of carboxylester lipase adsorption to surfaces. 1. Chemical specificity. Biochemistry 26:8423–8429CrossRefPubMedGoogle Scholar
  79. Tsujita T, Muderhwa JM, Brockman HL (1989) Lipid-lipid interactions as regulators of carboxyl esterase activity. J Biol Chem 264:8612–8618PubMedGoogle Scholar
  80. van Tilbeurgh H, Egloff MP, Martinez C, Rugani N, Verger R, Cambiliau C (1993) Interfacial activation of the lipase – procolipase complex by mixed micelles revealed by X-ray crystallography. Nature 362:814–820CrossRefPubMedGoogle Scholar
  81. Verger R, De Haas GH (1973) Enzyme reactions in a membrane model. 1. A new technique to study enzyme reactions in monolayers. Chem Phys Lipids 10:127–136CrossRefPubMedGoogle Scholar
  82. Verger R, de Haas GH (1976) Interfacial enzyme kinetics of lipolysis. Annu Rev Biophys Bioeng 5:77–117CrossRefPubMedGoogle Scholar
  83. Verger R, Rietsch J, Van Dam-Mieras MCE, de Haas GH (1976) Comparative studies of lipase and phospholipase A2 acting on substrate monolayers. J Biol Chem 251:3128–3133PubMedGoogle Scholar
  84. Verkleij AJ, Zwaal FRA, Roelofsen B, Comfurius P, Kastelijn D, Van Deenen LLM (1973) The asymmetric distribution of phospholipids in the human red cell membrane. Biochim Biophys Acta 323:178–193CrossRefPubMedGoogle Scholar
  85. Wiggins P, Phillips R (2005) Membrane-protein interactions in mechanosensitive channels. Biophys J 88:880–902PubMedCentralCrossRefPubMedGoogle Scholar
  86. Wilcox RW, Thuren T, Sisson P, Schmitt JD, Kennedy M, Mosely W (1993) Regulation of rate hepatic lipase by the composition of monomolecular film lipid. Biochemistry 32:5752–5758CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Food ScienceUniversity of Wisconsin-MadisonMadisonUSA

Personalised recommendations