Water Transport Across Cell Membranes

Abstract

This chapter is focused on the pathways and molecular mechanisms of water transport across the plasma membrane of animal cells. We discuss basic principles of water transport, including diffusion and osmosis and apply these concepts to the case of cell‐membrane water transport. The general conclusion is that diffusion and osmosis can explain water transport and that other mechanisms (e.g. cotransport) are less likely. Concerning the pathways for water movement across the plasma membrane, we consider the lipid bilayer, water‐selective pores (aquaporins – AQPs), nonselective larger pores, ion channels and membrane carriers. We conclude that the lipid bilayers and AQPs are the main pathways for transmembrane water fluxes, by solubility–diffusion and single‐file transport, respectively. Cell‐membrane water permeability varies considerably from cell to cell; high permeability denotes a fluid lipid bilayer and expression of AQPs. Low water permeability occurs when there is no aquaporin expression and membrane is rich in cholesterol.

Key Concepts:

  • Water transport across cell membranes occurs by diffusion and osmosis.

  • The effective osmolality of a biological fluid is determined by the total solute concentrations and the solutes’ permeabilities, relative to water.

  • The cell‐membrane osmotic water permeability varies from cell to cell, depending on the composition of the lipid bilayer and the presence or absence of water pores.

  • The two main pathways for plasma‐membrane water transport are the lipid bilayer and water‐selective pores (aquaporins).

  • Aquaporins are a large family of water pores; some isoforms are water‐selective whereas others are permeable to small solutes.

  • Aquaporin 1 (AQP1), the best studied isoform, is present in the membrane as a tetramer; each monomer has a water pore.

  • The pore of AQP1 is long and narrow (c. 2.8 Å diameter); water molecules lose their hydrogen bonds and permeate in single file.

  • AQP‐mediated water permeability appears to be regulated mostly by controlling the number of molecules present in the membrane. Regulation of the ‘opening’ of the pores has also been proposed for some isoforms.

  • AQP1 genetic deletion in mice causes profound alterations of renal function, consistent with a major physiological role of this protein.

Keywords: water transport; diffusion; osmosis; permeability; pores; cell membranes; aquaporin

Figure 1.

Water diffusion across a lipid membrane separating solutions of identical compositions and permeable to water, but not solute (semipermeable membrane). Solutes denoted by blue dots, selected water molecules by open circles. The box on the top left side denotes water self‐diffusion (i.e. random motion by thermal agitation). Water diffusion results in collisions of water molecules with the membrane and permeation by solubility diffusion. In as much as the solute concentrations are the same on both sides, the water chemical potentials are also the same. Thus, the unidirectional fluxes are the same in both directions (middle box) and the net flux is zero. When the water chemical potentials differ, there is a net water flux from the side of higher water chemical potential (lower solute concentration).

Figure 2.

Osmotic equilibrium. A ‘cell’ filled with a concentrated solution of impermeant solute (blue dots) is suspended in a dilute solution of the same solute. The differences in solute concentration create a difference in osmotic pressure across the membrane (Δπ), causing a net flow of water (open circles) into the cell, raising its hydrostatic pressure (measured from the difference in fluid height, ΔP). Osmotic equilibrium is reached when ΔP=Δπ (see text).

Figure 3.

Proposed mechanism of osmotic water flow across a porous membrane. The driving force is a difference in osmotic pressure (solute present on the right side only). Top: because the solute cannot enter the pore, there is a sharp fall in water concentration (Cw) at the solution‐facing mouth of the pore. Middle: this creates an imbalance in water fluxes across the interface: more water molecules leave than enter the pore, and thus the hydrostatic pressure (P) falls within the pore, creating a driving force for water flux from left to right. Bottom: the net driving force is the water chemical potential (μw), proportional to the sum of hydrostatic and osmotic pressures.

Figure 4.

Proposed water transport pathways across plasma membranes. (a) Solubility–diffusion across the phospholipid bilayer. The water permeability increases with the fluidity of the membrane. (b) Permeation via narrow pores (aquaporins) by single file. (c) Permeation via wide pores by viscous flow governed by Pouiseuille's law. (d) Permeation via ion channels: single file of water molecules separated by ions. (e) Permeation through carriers: water is contained in the carrier together with substrate(s) and cotransported by a conformational change. As discussed in the text, permeation through the lipid bilayers and aquaporins are the two main mechanisms. Open circles, water molecules and filled circles, solute molecules.

Figure 5.

Ribbon representation of a human AQP1 monomer viewed from the extracellular side. The amino acid residues surrounding the pore are shown in spherical representation (yellow), and are (starting clockwise from the asterisk): Asn76, Asn192, Leu75, Phe24, Ile60, Val176, Leu149 and Ile191. The minimum diameter of the pore is approximately 2.8 Å (a water molecule's molecular diameter is approximately 2.75 Å). In the plasma membrane AQP1 forms tetramers, with each subunit contributing a water pore, see text.

close

References

Agre P (2004) Nobel lecture. Aquaporin water channels. Bioscience Reports 24: 127–163.

Boron WF (2010) Sharpey–Schafer lecture: gas channels. Experimental Physiology 95: 1107–1130.

Charron FM, Blanchard MG and Lapointe J‐Y (2006) Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport. Biophysical Journal 90: 3546–3554.

Finkelstein A (1986) Water Movement Through Lipid Bilayers, Pores and Plasma Membranes. Theory and Reality. New York: Wiley.

Fu D, Libson A, Miercke LJ et al. (2000) Structure of a glycerol‐conducting channel and the basis for its selectivity. Science 290: 481–486.

Gonen T and Walz T (2006) The structure of aquaporins. Quarterly Reviews of Biophysics 4: 361–396.

de Groot BL and Grubmüller H (2005) The dynamics and energetics of water permeation and proton exclusion in aquaporins. Current Opinion in Structural Biology 15: 176–183.

Hirano Y, Okimoto N, Kadohira I et al. (2010) Molecular mechanisms of how mercury inhibits water permeation through aquaporin‐1: understanding by molecular dynamics simulation. Biophysics Journal 98: 1512–1519.

Ho JD, Yeh R, Sandstrom A et al. (2009) Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance. Proceedings of the National Academy of Sciences of the United States of America 106: 7437–7442.

Hub JS and de Groot BL (2008) Mechanism of selectivity in aquaporins and aquaglyceroporins. Proceedings of the National Academy of Sciences of the United States of America 105: 1198–1203.

Ikeda M, Beitz E, Kozono D et al. (2002) Characterization of aquaporin‐6 as a nitrate channel in mammalian cells. Journal of Biological Chemistry 277: 39873–39879.

Ishibashi K (2006) Aquaporin subfamily with unusual NPA boxes. Biochimica et Biophysica Acta 1758: 989–993.

Ishibashi K, Hara S and Kondo S (2009) Aquaporin water channels in mammals. Clinical and Experimental Nephrology 13: 107–117.

Jung JS, Preston GM, Smith BL, Guggino WB and Agre P (1994) Molecular structure of the water channel through aquaporin CHIP: the tetrameric‐hourglass model. Journal of Biological Chemistry 269: 14648–14654.

King LS, Kozono D and Agre P (2004) From structure to disease: the evolving tale of aquaporin biology. Nature Reviews Molecular Cell Biology 5: 687–698.

Loo DD, Wright EM and Zeuthen T (2002) Water pumps. Journal of Physiology (London) 542: 53–60.

Macey RI (1984) Transport of water and urea in red blood cells. American Journal of Physiology 246: C195–C203.

MacKinnon R (2003) Potassium channels. FEBS Letters 555: 62–65.

Magni F, Sarto C, Ticozzi D et al. (2006) Proteomic knowledge of human aquaporins. Proteomics 6: 5637–5649.

Nielsen S, Kwon T‐H, Frøkiær J and Agre P (2007) Regulation and dysregulation of aquaporins in water balance disorders. Journal of Internal Medicine 261: 53–64.

Nilius B (2004) Is the volume‐regulated anion channel VRAC a “water‐permeable” channel? Neurochemistry Research 29: 3–8.

Roux B and Schulten K (2004) Computational studies of membrane channels. Structure (Cambridge) 12: 1343–1351.

Sansom MSP (1998) Models and simulations of ion channels and related membrane proteins. Current Opinion in Structural Biology 8: 237–244.

Sui H, Han BG, Lee JK, Walian P and Jap BK (2001) Structural basis of water‐specific transport through the AQP1 water channel. Nature 414: 872–878.

Törnroth‐Horsefield S, Hedfalk K, Fischer G et al. (2010) Structural insights into eukaryotic aquaporin regulation. FEBS Letters 584: 2580–2588.

Verkman AS (1989) Mechanisms and regulation of water permeability in renal epithelia. American Journal of Physiology 257: C837–C850.

Verkman AS (2006) Roles of aquaporins in kidney revealed by transgenic mice. Seminars in Nephrology 26: 200–208.

Verkman AS (2009) Aquaporins: translating bench research to human disease. Journal of Experimental Biology 212: 1707–1715.

Walz T, Hirai T, Murata K et al. (1997) The three‐dimensional structure of aquaporin‐1. Nature 387: 624–626.

Yu J, Yool AJ, Schulten K and Talkhorshid E (2006) Mechanism of gating and ion conductivity of a possible tetrameric pore in aquaporin‐1. Structure 14: 1411–1423.

Zeuthen T (2010) Water‐transporting proteins. Journal of Membrane Biology 234: 57–73.

Further Reading

Fu D and Lu M (2007) The structural basis of water permeation and proton exclusion in aquaporins. Molecular Membrane Biology 24: 366–374.

Ishibashi K, Kondo S, Hara S and Morishita Y (2011) The evolutionary aspects of aquaporin family. American Journal of Physiology Regulatory Integrative and Comparative Physiology 300: R566–R576.

Mathai JC and Zeidel ML (2007) Measurement of water and solute permeability by stopped‐flow fluorimetry. Methods in Molecular Biology 400: 323–332.

Rawicz W, Smith BA, McIntosh TJ, Simon SA and Evans E (2008) Elasticity, strength, and water permeability of bilayers that contain raft microdomain‐forming lipids. Biophysical Journal 94: 4725–4736.

Reuss L (2008) Mechanisms of water transport across cell membranes and epithelia. In: Alpern RJ and Hebert SC (eds) The Kidney, Physiology and Pathophysiology, 4th edn. Amsterdam: Elsevier/Academic Press.

Rojek A, Praetorius J, Frøkjaer J, Nielsen S and Fenton RA (2007) A current view of the mammalian aquaglyceroporins. Annual Review of Physiology 70: 301–327.

Verkman AS (2011) Aquaporins at a glance. Journal of Cell Science 124: 2107–2112.

Wang Y, Shaikh SA and Tajkhorshid E (2010) Exploring transmembrane diffusion pathways with molecular dynamics. Physiology 25: 142–154.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Reuss, Luis(Jan 2012) Water Transport Across Cell Membranes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020621.pub2]