Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)

This article is in need of attention from a psychologist/academic expert on the subject.
Please help recruit one, or improve this page yourself if you are qualified.
This banner appears on articles that are weak and whose contents should be approached with academic caution
File:Finite Element Model.jpg

Mechanosensitive channels or mechanosensitive ion channels are membrane proteins capable of responding to mechanical stress over a wide dynamic range of external mechanical stimuli [2] [3] [4] [5] [6] .[7] They are found in prokaryotes and eukaryotes. The channels vary in selectivity for the permeating ions from nonselective between anions and cations in bacteria, to cation selective allowing passage Ca2+, K+ and Na+ in eukaryotes, and highly selective K+ channels in bacteria and eukaryotes.

All organisms, and apparently all cell types, sense and respond to mechanical stimuli.[8] MSCs function as mechanotransducers capable of generating both electrical and ion flux signals as a response to external or internal[9] stimuli.[10] Under extreme turgor in bacteria, non selective MSCs such as MSCL and MSCS serve as safety valves to prevent lysis. In specialized cells of the higher organisms, other types of MSCs are probably the basis of the senses of hearing and touch and sense the stress needed for muscular coordination. However, none of these channels have been cloned. MSCs also allow plants to distinguish up from down by sensing the force of gravity. MSCs are not pressure-sensitive, but sensitive to local stress, most likely tension in the surrounding lipid bilayer.[11]


Mechanosensitive channels were discovered in 1983 in the skeletal muscle of the chick[12] by Falguni Guharay and Frederick Sachs.[13] They were also observed (pub. 1986) in Xenopus oocytes,[14] and frequently studied since that time[15] [16] [17] [18] [19] [20] [21] [22] [23] [24] .[25] Since then, MS channels have been found in cells from bacteria to humans:[26] they are now known to be present in such kingdoms as the Archaea, Bacteria, Plantae, Fungi and Eukarya.[27] In the decades since the discovery of MS, the understanding of their structure and function has increased greatly, and several have been cloned. Specifically, the cloned eukaryotic mechanosensitive channels include the K+ selective 2P domain channels [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] and the recently cloned cation selective PIEZO family [42] [43] [44] [45] [46] .[47]


MS can be classified based on the type of ion to which they are permeable.

Cation Selective MSCs: As the name suggests, they exhibit a selective permeability for positive ions with the most selective channels being those for K+. The most common eukaryotic MSCs are cation selective passing Na+, K+ and Ca+ but not Mg+. They have a single channel conductance range (25-35 pS) and they are blocked by trivalent ion Gadolinium. The K selective MSCs such as TREK-1 are not blocked by Gd+3.[48]

Anion Channels: they exhibit a significant permeability for negative ions, and are not predominant as cation MS. They have a large conductance range (> 300pS).

Non Selective ion channels: As the name indicates, they do not differentiate between positive and negative channels those are more common to Archaea and Bacteria, but rarely found in Eukarya.[49]

Gating MechanismEdit

Although MS vary in many aspects, structures and functions, all the MS studied to date share an important feature: in a process called gating, they all open in a pore-like manner when protein channels are activated by a mechanical stimulus. There are currently two models of the gating process that explain how membrane-activated ion channels open.

File:Stretch model,.jpg

Lipid bilayer Tension or stretch model:[51] In this model tension in the lipid bilayer triggers conformational changes, thus leading to the opening of the channels. The tension perceived by the protein comes from the lipids. It has been demonstrated that the tension/stretch profile in the lipid bilayer is originated by membrane curvature and bilayer-protein hydrophobic mismatch.[52]

File:Spring-like model.jpg

Spring-like Tether model: In this model a spring-like tether is attached directly to the MS channel and can be present in either the cytoskeleton or the extracellular matrix linking these elements together. When external stimuli deflect the tether the displacement opens the channel.[50] This particular mechanism has been demonstrated to be the responsible for gating hair cells which are responsible for hearing in vertebrates.[53]

Bacterial MSEdit

Bacterial MS channels were first discovered by patch-clamp experiments in E. coli.[54] They have been classified based on their conductance as mini (MscM), small (MscS) and large (MscL). These channels function in tandem-mode and are responsible of turgor regulation in bacteria; when activated by changes in the osmotic pressure. MscM is activated first at really low pressures followed by MscS, and finally MsCL being the last chance of survival during osmotic shock. Their task was demonstrated when bacteria missing both MscS and MscL was lysed after exposure to osmotic downshocks.[55]

MscS: Small conductance mechanosensitive channel.

File:MscS close state.jpg

The main conductance is 1nS in buffer solution. Channel-proteins have been found in gram positive and gram negative bacteria, archaea and plants. MscS channel was found after studies in E. coli spheroplasts.[52] The identification of the gene family necessitated for MS of small conductance was as two different channels. YggB encoding MscS and KefA encoding MscK in E. coli further confirm its role osmotic regulation. Mutagenesis studies showed that when both genes YggB and KefA were deleted MscS lost its function, but maintain MscL and MscM, but mutants deficient of YggB and MscL showed that the function of those channel is to open in respond to pressure range right before cell rupture.[56]

The 3D structure of this channel at closed state was elucidated after the crystallography study by Bass et al.[57] which showed that at resolution of 3.9 Å this 31kDa protein is an homoheptamer forming a channel with 80 Å of diameter and 120 Å in length, each subunit contains three transmembrane domains (TM1, TM2, and TM3) with the N-terminal facing the periplasm and the C-terminal embedded in the cytoplasm. The TM3 is highly conserved in MscS family and it is thought to play an important role in MS prokaryotic gating.[58] MscS is a small protein composed of 286 amino acid residues activated by both tension in the lipid bilayer and voltage; in 2002 Vasquez et al.[59] detailed this process and showed that during the change from closed state to open state the TM1 tilt and rotate making TM2 being exposed to the membrane and the TM3 helices expand, tilt, and rotate. During the rearrangement the confined part of the pore was measured as 11 Å, and water molecules were more accessible to the TM3. The two transmembrane domains are in continuous contact with the lipid bilayer and are thought to be the sensor for the tension in the lipid bilayer as well as sensor for voltage because of the three arginine residues present in those domains.[60]

Although MscS is activated by voltage it has been demonstrated that, voltage itself is insufficient to open the channel, thus functioning in a cooperative manner with the channel. The more positive voltage, the higher the probabilities of opening the channel as long as pressure over the threshold is still applied in the system; the performance of this channel at higher voltage has not been completely understood. MscS has a small affinity for negative ions including Cl-, and glutamate.[61]

MscL: Large conductance mechanosensitive channel.

File:MscL close state.jpg

In bacteria MscL was the first MS channels cloned and sequenced, and is by far one of the most studied channels. The gene encoding MscL protein is trkA and it is located in the inner membrane of the E. coli. The protein is 17 KDa, and consists of 136 amino acids; mostly hydrophobic residues resulting in two hydrophobic segments, however molecular weight of the functional channel is presumed to be 60-70 KDa from gel filtration experiments, suggesting oligomerization. As a common feature no cysteines residues are present in this channel.[62]

In 1998 the homolog MscL from mycobacterium tuberculosis Tb-MscL was elucidated at closed state by X ray crystallography at 3.5 Å resolution. The protein is a homopentamer composed mostly of helical regions trans orientation of the helices with respect to the bilayer, with two domains: the cytoplasmic and the transmembrane. The channel is 85 Å in length, 35 Å and 50 Å for the cytoplasmic transmembrane domain respectively and 50 Å in diameter. The helices cross the membrane twice with both the C-terminal and the N-terminal, thus having two transmembrane domains TM1 and TM2 being TM1 the most conserved region among MscL proteins especially at the N-terminal region.[63] It is located in the cytoplasm and forms a α-hydrophobic helix called S1; the region between the transmembrane domains form a loop that is divided into two regions: S2 a glycine-proline rich region and S3 a short helical section.[64] Also interestingly the secondary structure of the protein is resistant to thermal denaturation still in the presence of SDS.[65]

During the activation of the prokaryotic MscL by tension in the lipid bilayer an intermediate state was determined. The S1 segments form a bundle when the structure is in the closed state, and the crosslinking of S1 segments prevents the opening of the channel. When tension is applied to the membrane the transmembrane barrel-like structure expand and stretch apart the region S1-TM1 allowing the channel to open.[66] The size of the pore at open state is approximately 25Å. The transition from closed to intermediate state is accompanied by small movements of the TM1; further transitions to the open stated are characterized by big rearrangements in both the TM1 and TM2.[67]

Role of lipid bilayer in MSEdit

The lipid bilayer is an important structure in all living cells; it has many functions such as separation of compartments, and signaling among others. In the case of the prokaryotic protein channels MscS and MscL both are gated by tension in the lipid bilayer, thus suggesting an important role in such a complex structures.

The tension in the membrane bilayer has been extensively studied, simple intrinsic properties of the lipids can account for the contributions in the free energy of the open, intermediate, and close state of the MS channels. The bilayer possess different features that allows it to transducer tension and to prevent exhaustive deformations, the first one is “in plane fluidity of the lipid bilayer” meaning that any in plane tension in the lipid bilayer is felt homogenously in the absence of cytoskeleton interactions. The lipid molecules have a specific space in between them, preventing the bilayer from any changes.[68]

The contribution of membrane deformation in the gating of MS channels can be divided in two types: the deformation of the plane of the bilayer, and the deformation of the thickness of the bilayer. Also during any process involving changes in the structure, the free energy of the process itself is also an important factor. During gating the major processes that account for this event are: hydrophobic mismatch, and membrane curvature. It has been calculated that the free energy of the tension in the lipid bilayer is similar to the energy needed for gating the channels.[69]

A different study showed that the length of the hydrophobic tail affects its functioning as well as supporting the different states, Phosphatidylcholine (PC) 18 stabilizes better the open state of the MscL channel, PC 14 stabilizes the intermediate state, and a mixture of PC 18 and lysophosphatidylcholine (LPC) stabilizes the closed state,[67] suggesting that the bilayer thickness (for carbon tail lengths of 16, 18 and 20) affects channel function. In conclusion the energy from the environment of the membrane plays an important role in the total energy of channel gating.

Physiological role of MSEdit

MS channels are ubiquitously expressed in the membrane of prokaryotes suggesting their significance. In Bacteria and Archaea the function of these channels is conserved and it has been demonstrated that they play a role in turgor regulation. In Eukarya MS channels are involved in all five senses. The main family is TRP, and one good example is hair cells involved in the hearing process. When a wave of sound deflects the stereocilia, the channel opens. This is an instance of the Spring-like Tether gating mechanism. Recent studies have revealed a new role of mechanosensitive pathways in which naive mesenchymal stem cells are committed to a particular lineage based on the elasticity of its surrounding matrix.[70]

Some MS channels that have been cloned and characterized. Data adapted from Martinac, 2001[71]
Channel Source Gating mechanism Physiological role
MscL Bacteria Lipid bilayer Turgor regulation and cell growth
MscS Bacteria Lipid bilayer Turgor regulation and cell growth
MscMJ Archaea Lipid bilayer Turgor regulation
MEC4 C. elegans Tether Touch
TRPY Fungi Bilayer Turgor regulation
TRECK-1 Mammalian Bilayer Resting membrane potential
TRP-1 Hair cell Tether Hearing

MS have also been suggested as a potential target for antibiotics, the reasoning behind this idea is that both McsS and MscL are highly conserved among prokaryotes, but their homologs have not been found in animals[72] making them an exceptional potential for further studies.

Techniques used to study MSEdit

This is a short list of the most frequently techniques used to study the properties, function, mechanism and other features of these channels.

• Patch-clamp: Single cell recording.


• Molecular dynamics simulation: determination of the atomic fluctuation of the system.

• Atomic force Microscopy: mechanical forces of the membrane.

• Micropipette Aspiration: Pressure to cells.

• 3D simulations

• Mutagenesis

MS DiseasesEdit

• Polycystic kidney disease.

• Atrial fibrillation

Abnormalities in the function of MS channels can cause:[27]

I. Neuronal disease

II. Muscular degeneration.

III. cardiac arrhythmias

IV. Hypertension.

See alsoEdit


  1. Tang Y, Cao G, Chen X, et al. (2006). A finite element framework for studying the mechanical response of macromolecules: application to the gating of the mechanosensitive channel MscL. Biophys J 91 (91): 1248–63.
  2. Sukharev, S, Sachs, F. (2012). Molecular Force Transduction by Ion Channels: diversity and unifying principles. J. Cell Sci. 125 (13): 1–9.
  3. Gottlieb, P., Sachs, F (2012). The sensation of stretch. Nature 463 (7278): 163–164.
  4. Sachs, F (2010). Stretch activated Ion Channels; What are They. Physiology 25 (1): 50–56.
  5. Bowman, C. L., Gottlieb, P. A., Suchyna, T. M., Murphy, Y. K. & Sachs, F. (2007). Mechanosensitive ion channels and the peptide inhibitor GsMTx-4: History, properties, mechanisms and pharmacology. Toxicon 49 (2): 249–270.
  6. Suchyna, T. M., Sachs, F. (2007). Mechanosensitive channel properties and membrane mechanics in mouse dystrophic myotubes. J Physiol 581 (Pt 1): 369–387.
  7. Markin, V., Sachs, F. (2006). Thermodynamics of mechanosensitivity. Current Topics in Membranes and Transport 1 (2): 110.
  8. (2005). A possible unifying principle for mechanosensation. Nature 436 (7051): 647–54.
  9. Suchyna, T, Sachs, F. (2007). Mechanical and electrical properties of membranes from dystrophic and normal mouse muscle. J.Physiol.(Lond) 581 (Pt 1): 369–387.
  10. Hackney CM, Furness DN. "Mechanotransduction in vertebrate hair cells: structure and function of the stereociliary bundle. AmJ Physiol 1995; 268:C1–138.
  11. (2004). Thermodynamics of mechanosensitivity. Physical Biology 1 (2): 110.
  12. (July 1984). Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle. J. Physiol. (Lond.) 352: 685–701.
  13. Guharay, F., Sachs, F. (1985). Mechanotransducer ion channels in chick skeletal muscle: the effects of extracellular pH. Journal of Physiology (Lond.) 353: 119–134.
  14. Methfessel, C., et al. (1986). Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels. Pflugers Archiv.European Journal of Physiology 407 (6): 577–588.
  15. Zhang, Y., Gao, F., Popov, V. L., Wen, J. W. & Hamill, O. P. (2000). Mechanically gated channel activity in cytoskeleton-deficient plasma membrane blebs and vesicles from Xenopus oocytes. Journal of Physiology 523 (Pt 1): 117–130.
  16. Zhang, Y., Hamill, O. P. (2000). Calcium-, voltage- and osmotic stress-sensitive currents in Xenopus oocytes and their relationship to single mechanically gated channels. Journal of Physiology (Lond) 523: 83–99.
  17. Zhang, Y., Hamill, O. P. (2000). On the discrepancy between whole-cell and membrane patch mechanosensitivity in Xenopus oocytes. Journal of Physiology (Lond) 523: 101–115.
  18. Hamill, O. P., McBride, D. W., Jr. (1997). Mechanogated channels in Xenopus oocytes: different gating modes enable a channel to switch from a phasic to a tonic mechanotransducer. Biological Bulletin 192 (1): 121–122.
  19. Hamill, O. P, McBride, D. W. J. (1996). Membrane voltage and tension interactions in the gating of the mechano-gated cation channel in xenopus oocytes. Biophysical Journal 70: A348.
  20. Wilkinson, N. C., McBride, D. W. & Hamill, O. P. (1996). Testing the putative role of a mechano-gated channel in testing Xenopus oocyte maturation, fertilization and tadpole development. Biophysical Journal 70: A349.
  21. Lane, J. W., McBride, D. W., Jr. & Hamill, O. P. Ionic effects on amiloride block of the mechanosensitive channel in Xenopus oocytes" British Journal of Pharmacology 108, 116-119 (1993).
  22. (1992). Rapid adaptation of single mechanosensitive channels in Xenopus oocytes. Proceedings of the National Academy of Sciences of the United States of America 89 (16): 7462–7466.
  23. (1992). Structure-activity relations of amiloride and its analogues in blocking the mechanosensitive channel in Xenopus oocytes. British Journal of Pharmacology 106 (2): 283–286.
  24. (1992). Pressure-clamp: a method for rapid step perturbation of mechanosensitive channels. Pflugers Archiv. European Journal of Physiology 421 (6): 606–612.
  25. Lane, J. W., McBride, D. & Hamill, O. P. (1991) Amiloride block of the mechanosensitive cation channel in Xenopus oocytes. Journal of Physiology (London) 441, 347-366 .
  27. 27.0 27.1
  28. Peyronnet, R. et al. Mechanoprotection by Polycystins against Apoptosis Is Mediated through the Opening of Stretch-Activated K2P Channels. Cell Reports 1 (in press), 241-250 (2012)
  29. (2007). Up- and down-regulation of the mechano-gated K-2P channel TREK-1 by PIP2 and other membrane phospholipids. Pflugers Archiv-European Journal of Physiology 455 (1): 97–103.
  30. (2007). The neuronal background K2P channels: focus on TREK1. Nature Reviews Neuroscience 8 (4): 251–261.
  31. Chemin, J. et al. in Mechanosensitive Ion Channels, Pt B Vol. 59 Current Topics in Membranes (ed O.P. Hamill) Ch. 7, 155-170 (Academic Press, 2007).>
  32. (2006). Desensitization of mechano-gated K-2P channels. Proceedings of the National Academy of Sciences of the United States of America 103 (18): 6859–6864.
  33. (2005). Lysophosphatidic acid-operated K+ channels. Journal of Biological Chemistry 280 (6): 4415–4421.
  34. (2005). Cross-talk between the mechano-gated K-2P channel TREK-1 and the actin cytoskeleton. EMBO Reports 6 (7): 642–648.
  35. Honore, E., Patel, A. A., Kohl, P., Franz, M. R. & Sachs, F. in Cardiac Mechano-Electric Feedback and Arrhythmias: From Pipette to Patient (Elsevier 2004)
  36. Maingret, F., Honore, E., Lazdunski, M. & Patel, A. J. (2002) Molecular basis of the voltage-dependent gating of TREK-1, a mechano-sensitive K(+) channel. Biochem.Biophys Res.Commun 292, 339-346 .
  37. (2001). Lipid and mechano-gated 2P domain K(+) channels. Curr.Opin.Cell Biol 13 (4): 422–428.
  38. (2001). Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci 24 (6): 339–346.
  39. (2000). Lysophospholipids open the two-pore domain mechano-gated K(+) channels TREK-1 and TRAAK. Journal of Biological Chemistry 275 (14): 10128–10133.
  40. (1999). Inhalational anesthetics activate two-pore-domain background K+ channels. Nat.Neurosci 2 (5): 422–426.
  41. (1998). A mammalian two pore domain mechano-gated S-like K+ channel. EMBO Journal 17 (15): 4283–4290.
  42. (2012). Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483 (7388): 176–81.
  43. (2012). The role of Drosophila Piezo in mechanical nociception. Nature 483 (7388): 209–12.
  44. (2010). Are Essential Components of Distinct Mechanically Activated Cation Channels. Science 330 (6000): 55–60.
  45. (2012). Properties of a cation selective mechanical channel. Channels 6 (4): 1–6.
  46. (2012). CELL BIOLOGY The sensation of stretch. Nature 483 (7388): 163–164.
  47. (2011). The Mechanosensitive Ion Channel Piezo1 Is Inhibited by the Peptide GsMTx4. Biochemistry 50 (29): 6295–300.
  48. (2008). The mechano-gated K2P channel TREK-1. European Biophysics Journal 38 (3): 293–303.
  49. (1995). Mechanosensitive channels. Annu. Rev. Physiol 57: 333–53.
  50. 50.0 50.1 50.2 Lumpkin, E, Caterina M. (2006). Mechanisms of sensory transduction in the skin. Mechanisms of sensory transduction in the skin. 445 (7130): 445:858.
  51. (1991). Mechanosensitive ion channels as reporters of bilayer expansion. A theoretical model. Biophys. J 60 (5): 1120–1127.
  52. 52.0 52.1 (2002). Structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418 (6901): 942–8.
  53. (1997). Induced membrane hypo /hyper mechanosensitivity A limitation of patch-clamp recording. Ann. Rev. Physiol 59: 621–631.
  54. Martinac B, Buechner M, Delcour AH, Adler J, Kung C: Pressuresensitive ion channel in Escherichia coli" Proc Natl Acad Sci USA 1987, 84:2297-2301.
  55. (2003). Structure and mechanism in prokaryotic mecahnosensitive channels. Curr. Opin. Struct. Biol 13 (4): 432–442.
  56. (1999). Protection of Escherichia coli cells againstextreme turgor by activation of MscS and MscL mechanosensitivechannels: Identification of genes required for MscS activity. EMBO J 18 (7): 1730–1737.
  57. (2002). Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel. Science 29 (5598): 1582–1587.
  58. (2003). Two families of mechanosensitive channel proteins. Microbiol. Mol. Biol. Rev 67 (1): 66–85.
  59. (2008). A Structural mechanism for MscS gating lipid channels in bilayer. Science 321 (5893): 1210–14.
  60. (2002). Force and voltage sensors in one structure. Science 298 (5598): 1562–1563.
  61. (1997). MECHANOSENSITIVE CHANNELS OF ESCHERICHIA COLI: The MscL Gene, Protein, and Activities. Annu. Rev. Physiol 59: 633–57.
  62. (1994). A large mechanosensitive channel in E. coli encoded by MscL alone. Nature 368 (6468): 265–268.
  63. (1998). Structure of the MscL homologue from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science 282 (5397): 2220–2226.
  64. (1996). Membrane topology and multimeric structure of a mechanosensitive channel protein. EMBO J 15 (18): 4798–4805.
  65. (1998). Helicity, membrane incorporation, orientation, and thermalstability of the large conductance mechanosensitive ion channel from E.coli. Biochim. Byophys. Acta. 1: 131–140.
  66. (2001). The gating mechanism of the large mechanosensitive channel MscL. Nature 409 (6821): 720–724.
  67. 67.0 67.1 (2002). Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418 (6901): 942–948.
  68. (2004). Analytic models for mechanotransduction: Gating a mechanosensitive channel. Proc Natl Acad Sci U S A 101 (12): 4071–6.
  69. (2005). Membrane-protein interactions in mechanosensitivechannels. Biophys J 88 (2): 880–902.
  70. (2006). Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 126 (4): 677–689.
  71. (2001). Molecular basis of mechanotransduction in living cells. Physiol. Rev 81 (2): 685–740.
  72. (2005). The effects of parabens on the mechanosensitive channels. Eur Biophys. J 34 (5): 389–396.

The following is not referenced in the article, and/or is in conflict with Engler, A. etal,2006:

29. Perozo E, Kloda A, Cortes DM, et al. Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating. Nature Structural & Molecular Biology 2002; 9:696–703.

This page uses Creative Commons Licensed content from Wikipedia (view authors).

Ad blocker interference detected!

Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers

Wikia is not accessible if you’ve made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected.