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Physiological Reviews, Vol. 81, No. 2, April 2001, pp. 685-740
Copyright ©2001 by the American Physiological Society
Physiology and Biophysics, University Of Texas Medical Branch, Galveston, Texas; and Department of Pharmacology, University Of Western Australia, Nedlands, West Australia
Hamill, Owen P. and
Boris Martinac.
Molecular Basis of Mechanotransduction in Living Cells. Physiol. Rev. 81: 685-740, 2001.
The simplest cell-like structure, the lipid
bilayer vesicle, can respond to mechanical deformation by elastic
membrane dilation/thinning and curvature changes. When a protein is
inserted in the lipid bilayer, an energetic cost may arise because of
hydrophobic mismatch between the protein and bilayer. Localized changes
in bilayer thickness and curvature may compensate for this mismatch.
The peptides alamethicin and gramicidin and the bacterial membrane protein MscL form mechanically gated (MG) channels when inserted in
lipid bilayers. Their mechanosensitivity may arise because channel
opening is associated with a change in the protein's
membrane-occupied area, its hydrophobic mismatch with the bilayer,
excluded water volume, or a combination of these effects. As a
consequence, bilayer dilation/thinning or changes in local membrane
curvature may shift the equilibrium between channel conformations.
Recent evidence indicates that MG channels in specific animal cell
types (e.g., Xenopus oocytes) are also gated directly by
bilayer tension. However, animal cells lack the rigid cell wall that
protects bacteria and plants cells from excessive expansion of their
bilayer. Instead, a cortical cytoskeleton (CSK) provides a structural
framework that allows the animal cell to maintain a stable excess
membrane area (i.e., for its volume occupied by a sphere) in the form
of membrane folds, ruffles, and microvilli. This excess membrane provides an immediate membrane reserve that may protect the bilayer from sudden changes in bilayer tension. Contractile elements within the
CSK may locally slacken or tighten bilayer tension to regulate mechanosensitivity, whereas membrane blebbing and tight seal patch formation, by using up membrane reserves, may increase membrane mechanosensitivity. In specific cases, extracellular and/or CSK proteins (i.e., tethers) may transmit mechanical forces to the process
(e.g., hair cell MG channels, MS intracellular Ca2+
release, and transmitter release) without increasing tension in the
lipid bilayer.
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S. J Haug, D. G Welsh, and S. S Segal Sympathetic Nerves Inhibit Conducted Vasodilatation Along Feed Arteries during Passive Stretch of Hamster Skeletal Muscle J. Physiol., October 1, 2003; 552(1): 273 - 282. [Abstract] [Full Text] [PDF]
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S. Ben-Tabou De-Leon, E. Blotnick, and I. Nussinovitch Effects of osmotic swelling on voltage-gated calcium channel currents in rat anterior pituitary cells Am J Physiol Cell Physiol, October 1, 2003; 285(4): C840 - C852. [Abstract] [Full Text] [PDF]
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E. C. Y. Wang, J.-M. Lee, J. P. Johnson, T. R. Kleyman, R. Bridges, and G. Apodaca Hydrostatic pressure-regulated ion transport in bladder uroepithelium Am J Physiol Renal Physiol, October 1, 2003; 285(4): F651 - F663. [Abstract] [Full Text] [PDF]
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H. Magloire, F. Lesage, M.L. Couble, M. Lazdunski, and F. Bleicher Expression and Localization of TREK-1 K+ Channels in Human Odontoblasts Journal of Dental Research, July 1, 2003; 82(7): 542 - 545. [Abstract] [Full Text] [PDF]
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X.-L. Zhou, A. F. Batiza, S. H. Loukin, C. P. Palmer, C. Kung, and Y. Saimi The transient receptor potential channel on the yeast vacuole is mechanosensitive PNAS, June 10, 2003; 100(12): 7105 - 7110. [Abstract] [Full Text] [PDF]
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N. Bettache, L. Baisamy, S. Baghdiguian, B. Payrastre, P. Mangeat, and A. Bienvenue Mechanical constraint imposed on plasma membrane through transverse phospholipid imbalance induces reversible actin polymerization via phosphoinositide 3-kinase activation J. Cell Sci., June 1, 2003; 116(11): 2277 - 2284. [Abstract] [Full Text] [PDF]
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J. A. Maurer and D. A. Dougherty Generation and Evaluation of a Large Mutational Library from the Escherichia coli Mechanosensitive Channel of Large Conductance, MscL: IMPLICATIONS FOR CHANNEL GATING AND EVOLUTIONARY DESIGN J. Biol. Chem., May 30, 2003; 278(23): 21076 - 21082. [Abstract] [Full Text] [PDF]
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A. Kumar, A. J. Knox, and A. M. Boriek CCAAT/Enhancer-binding Protein and Activator Protein-1 Transcription Factors Regulate the Expression of Interleukin-8 through the Mitogen-activated Protein Kinase Pathways in Response to Mechanical Stretch of Human Airway Smooth Muscle Cells J. Biol. Chem., May 23, 2003; 278(21): 18868 - 18876. [Abstract] [Full Text] [PDF]
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A. P. Seale, N. H. Richman III, T. Hirano, I. Cooke, and E. G. Grau Evidence that signal transduction for osmoreception is mediated by stretch-activated ion channels in tilapia Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1290 - C1296. [Abstract] [Full Text] [PDF]
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K. Strange From Genes to Integrative Physiology: Ion Channel and Transporter Biology in Caenorhabditis elegans Physiol Rev, April 1, 2003; 83(2): 377 - 415. [Abstract] [Full Text] [PDF]
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P. Koprowski and A. Kubalski C Termini of the Escherichia coli Mechanosensitive Ion Channel (MscS) Move Apart upon the Channel Opening J. Biol. Chem., March 21, 2003; 278(13): 11237 - 11245. [Abstract] [Full Text] [PDF]
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J. Aleu, M. Martin-Satue, P. Navarro, I. P. de Lara, L. Bahima, J. Marsal, and C. Solsona Release of ATP induced by hypertonic solutions in Xenopus oocytes J. Physiol., February 15, 2003; 547(1): 209 - 219. [Abstract] [Full Text] [PDF]
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 X. Gasull, E. Ferrer, A. Llobet, A. Castellano, J. M. Nicolas, J. Pales, and A. Gual Cell Membrane Stretch Modulates the High-Conductance Ca2+-Activated K+ Channel in Bovine Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., February 1, 2003; 44(2): 706 - 714. [Abstract] [Full Text] [PDF]
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Y. Ou, P. Strege, S. M. Miller, J. Makielski, M. Ackerman, S. J. Gibbons, and G. Farrugia Syntrophin gamma 2 Regulates SCN5A Gating by a PDZ Domain-mediated Interaction J. Biol. Chem., January 10, 2003; 278(3): 1915 - 1923. [Abstract] [Full Text] [PDF]
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A. Koller and Z. Bagi On the role of mechanosensitive mechanisms eliciting reactive hyperemia Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2250 - H2259. [Abstract] [Full Text] [PDF]
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 N. E. Vlahakis, M. A. Schroeder, R. E. Pagano, and R. D. Hubmayr Role of Deformation-induced Lipid Trafficking in the Prevention of Plasma Membrane Stress Failure Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1282 - 1289. [Abstract] [Full Text] [PDF]
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R. E. Oswald, T. M. Suchyna, R. McFeeters, P. Gottlieb, and F. Sachs Solution Structure of Peptide Toxins That Block Mechanosensitive Ion Channels J. Biol. Chem., September 6, 2002; 277(37): 34443 - 34450. [Abstract] [Full Text] [PDF]
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C. M. Waters, P. H. S. Sporn, M. Liu, and J. J. Fredberg Cellular biomechanics in the lung Am J Physiol Lung Cell Mol Physiol, September 1, 2002; 283(3): L503 - L509. [Abstract] [Full Text] [PDF]
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G. L. Lyford, P. R. Strege, A. Shepard, Y. Ou, L. Ermilov, S. M. Miller, S. J. Gibbons, J. L. Rae, J. H. Szurszewski, and G. Farrugia alpha 1C (CaV1.2) L-type calcium channel mediates mechanosensitive calcium regulation Am J Physiol Cell Physiol, September 1, 2002; 283(3): C1001 - C1008. [Abstract] [Full Text] [PDF]
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K. Okada, P. C. Moe, and P. Blount Functional Design of Bacterial Mechanosensitive Channels. COMPARISONS AND CONTRASTS ILLUMINATED BY RANDOM MUTAGENESIS J. Biol. Chem., July 26, 2002; 277(31): 27682 - 27688. [Abstract] [Full Text] [PDF]
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