Sensing bilayer tension: bacterial mechanosensitive channels and their gating mechanisms

2011 ◽  
Vol 39 (3) ◽  
pp. 733-740 ◽  
Author(s):  
Ian R. Booth ◽  
Tim Rasmussen ◽  
Michelle D. Edwards ◽  
Susan Black ◽  
Akiko Rasmussen ◽  
...  
Keyword(s):  
Pore Diameter ◽  
Ionic Composition ◽  
Unique Property ◽  
Mechanosensitive Channel ◽  
Mechanosensitive Channels ◽  
Membrane Tension ◽  
Cellular Integrity ◽  
Sense And Respond ◽  
Cellular Behaviour ◽  
Lipid Interaction

Mechanosensitive channels sense and respond to changes in bilayer tension. In many respects, this is a unique property: the changes in membrane tension gate the channel, leading to the transient formation of open non-selective pores. Pore diameter is also high for the bacterial channels studied, MscS and MscL. Consequently, in cells, gating has severe consequences for energetics and homoeostasis, since membrane depolarization and modification of cytoplasmic ionic composition is an immediate consequence. Protection against disruption of cellular integrity, which is the function of the major channels, provides a strong evolutionary rationale for possession of such disruptive channels. The elegant crystal structures for these channels has opened the way to detailed investigations that combine molecular genetics with electrophysiology and studies of cellular behaviour. In the present article, the focus is primarily on the structure of MscS, the small mechanosensitive channel. The description of the structure is accompanied by discussion of the major sites of channel–lipid interaction and reasoned, but limited, speculation on the potential mechanisms of tension sensing leading to gating.

scholarly journals The Purified Mechanosensitive Channel TREK-1 Is Directly Sensitive to Membrane Tension

2013 ◽  
Vol 288 (38) ◽  
pp. 27307-27314 ◽  
Author(s):  
Catherine Berrier ◽  
Alexandre Pozza ◽  
Agnes de Lacroix de Lavalette ◽  
Solenne Chardonnet ◽  
Agnes Mesneau ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Mechanosensitive Channel ◽  
Positive Pressure ◽  
Mechanosensitive Channels ◽  
Membrane Tension ◽  
Animal Cells ◽  
Patch Clamp Recording ◽  
Electrophysiological Properties ◽  
Pressure Suction ◽  
Pore Domain

Mechanosensitive channels are detected in all cells and are speculated to play a key role in many functions including osmoregulation, growth, hearing, balance, and touch. In prokaryotic cells, a direct gating of mechanosensitive channels by membrane tension was clearly demonstrated because the purified channels could be functionally reconstituted in a lipid bilayer. No such evidence has been presented yet in the case of mechanosensitive channels from animal cells. TREK-1, a two-pore domain K+ channel, was the first animal mechanosensitive channel identified at the molecular level. It is the target of a large variety of agents such as volatile anesthetics, neuroprotective agents, and antidepressants. We have produced the mouse TREK-1 in yeast, purified it, and reconstituted the protein in giant liposomes amenable to patch clamp recording. The protein exhibited the expected electrophysiological properties in terms of kinetics, selectivity, and pharmacology. Negative pressure (suction) applied through the pipette had no effect on the channel, but positive pressure could completely and reversibly close the channel. Our interpretation of these data is that the intrinsic tension in the lipid bilayer is sufficient to maximally activate the channel, which can be closed upon modification of the tension. These results indicate that TREK-1 is directly sensitive to membrane tension.

scholarly journals Lipid–protein forces predict conformational changes in a mechanosensitive channel

2020 ◽  
Author(s):  
Csaba Daday ◽  
Bert L. de Groot
Keyword(s):  
Potassium Channel ◽  
Conformational Change ◽  
Conformational Changes ◽  
Mechanosensitive Channel ◽  
Computational Studies ◽  
Interaction Patterns ◽  
Membrane Tension ◽  
Lipid Interaction

AbstractThe mechanosensitive TREK-2 potassium channel, a member of the K2P family, has essential physiological roles and is, therefore, a pharmaceutical target. A combination of experimental and computational studies have established that of the two known conformations, “up” and “down”, membrane tension directly favors the “up” state, which displays a higher conductance. However, these studies did not reveal the exact mechanism by which the membrane affects the channel conformation. In this work, we show that changes in protein–lipid interaction patterns suffice in predicting this conformational change, and pinpoint potentially important residues involved in this phenomenon.

scholarly journals Cyclodextrins increase membrane tension and are universal activators of mechanosensitive channels

2021 ◽  
Vol 118 (36) ◽  
pp. e2104820118
Author(s):  
Charles D. Cox ◽  
Yixiao Zhang ◽  
Zijing Zhou ◽  
Thomas Walz ◽  
Boris Martinac
Keyword(s):  
Escherichia Coli ◽  
Conformational Changes ◽  
Functional Characterization ◽  
Mechanosensitive Channel ◽  
Mechanical Forces ◽  
Mechanosensitive Channels ◽  
Membrane Tension ◽  
Lipid Environment ◽  
Small Conductance

The bacterial mechanosensitive channel of small conductance (MscS) has been extensively studied to understand how mechanical forces are converted into the conformational changes that underlie mechanosensitive (MS) channel gating. We showed that lipid removal by β-cyclodextrin can mimic membrane tension. Here, we show that all cyclodextrins (CDs) can activate reconstituted Escherichia coli MscS, that MscS activation by CDs depends on CD-mediated lipid removal, and that the CD amount required to gate MscS scales with the channel’s sensitivity to membrane tension. Importantly, cholesterol-loaded CDs do not activate MscS. CD-mediated lipid removal ultimately causes MscS desensitization, which we show is affected by the lipid environment. While many MS channels respond to membrane forces, generalized by the “force-from-lipids” principle, their different molecular architectures suggest that they use unique ways to convert mechanical forces into conformational changes. To test whether CDs can also be used to activate other MS channels, we chose to investigate the mechanosensitive channel of large conductance (MscL) and demonstrate that CDs can also activate this structurally unrelated channel. Since CDs can open the least tension-sensitive MS channel, MscL, they should be able to open any MS channel that responds to membrane tension. Thus, CDs emerge as a universal tool for the structural and functional characterization of unrelated MS channels.

scholarly journals Cyclodextrins increase membrane tension and are universal activators of mechanosensitive channels

2021 ◽  
Author(s):  
Charles D Cox ◽  
Yixiao Zhang ◽  
Zijing Zhou ◽  
Thomas Walz ◽  
Boris Martinac
Keyword(s):  
Conformational Changes ◽  
Functional Characterization ◽  
Mechanosensitive Channel ◽  
Mechanical Forces ◽  
Mechanosensitive Channels ◽  
Membrane Tension ◽  
E Coli ◽  
Lipid Environment ◽  
Small Conductance

AbstractThe bacterial mechanosensitive channel of small conductance, MscS, has been extensively studied to understand how mechanical forces are converted into the conformational changes that underlie mechanosensitive (MS) channel gating. We showed that lipid removal by β-cyclodextrin can mimic membrane tension. Here, we show that all cyclodextrins (CDs) can activate reconstituted E. coli MscS, that MscS activation by CDs depends on CD-mediated lipid removal, and that the CD amount required to gate MscS scales with the channel’s sensitivity to membrane tension. CD-mediated lipid removal ultimately causes MscS desensitization, which we show is affected by the lipid environment. CDs can also activate the structurally unrelated MscL. While many MS channels respond to membrane forces, generalized by the ‘force-from-lipids’ principle, their different molecular architectures suggest that they use unique ways to convert mechanical forces into conformational changes. CDs emerge as a universal tool for the structural and functional characterization of unrelated MS channels.

scholarly journals Effect of TiO2 Nanotube Pore Diameter on Human Mesenchymal Stem Cells and Human Osteoblasts

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2117
Author(s):  
Juan Shong Khaw ◽  
Christopher R. Bowen ◽  
Sarah H. Cartmell
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Pore Diameter ◽  
Human Mesenchymal Stem Cells ◽  
Tio2 Nanotube ◽  
Human Stem Cells ◽  
Material Interfaces ◽  
Human Osteoblasts ◽  
Cellular Behaviour ◽  
20 Nm

The pore diameter of uniformly structured nanotubes can significantly change the behaviour of cells. Recent studies demonstrated that the activation of integrins is affected not by only the surface chemistry between the cell-material interfaces, but also by the features of surface nanotopography, including nanotube diameter. While research has been carried out in this area, there has yet to be a single systemic study to date that succinctly compares the response of both human stem cells and osteoblasts to a range of TiO2 nanotube pore diameters using controlled experiments in a single laboratory. In this paper, we investigate the influence of surface nanotopography on cellular behaviour and osseointegrative properties through a systemic study involving human mesenchymal stem cells (hMSCs) and human osteoblasts (HOBs) on TiO2 nanotubes of 20 nm, 50 nm and 100 nm pore diameters using in-vitro assessments. This detailed study demonstrates the interrelationship between cellular behaviour and nanotopography, revealing that a 20 nm nanotube pore diameter is preferred by hMSCs for the induction of osteogenic differentiation, while 50 nm nanotubular structures are favourable by HOBs for osteoblastic maturation.

Mechanosensitive Channels Gated by Membrane Tension

2008 ◽  
pp. 71-101 ◽  
Author(s):  
Paul Blount ◽  
Li Yuezhou ◽  
Paul C. Moe ◽  
Irene Iscla
Keyword(s):  
Mechanosensitive Channels ◽  
Membrane Tension

scholarly journals Connecting the Dots between Mechanosensitive Channel Abundance, Osmotic Shock, and Survival at Single-Cell Resolution

2018 ◽  
Vol 200 (23) ◽  
Author(s):  
Griffin Chure ◽  
Heun Jin Lee ◽  
Akiko Rasmussen ◽  
Rob Phillips
Keyword(s):  
Cell Survival ◽  
Single Cell ◽  
Osmotic Shock ◽  
Single Cells ◽  
Mechanosensitive Channel ◽  
Membrane Tension ◽  
Wild Type ◽  
Content Type ◽  
E Coli ◽  
Structural Methods

ABSTRACTRapid changes in extracellular osmolarity are one of many insults microbial cells face on a daily basis. To protect against such shocks,Escherichia coliand other microbes express several types of transmembrane channels that open and close in response to changes in membrane tension. InE. coli, one of the most abundant channels is the mechanosensitive channel of large conductance (MscL). While this channel has been heavily characterized through structural methods, electrophysiology, and theoretical modeling, our understanding of its physiological role in preventing cell death by alleviating high membrane tension remains tenuous. In this work, we examine the contribution of MscL alone to cell survival after osmotic shock at single-cell resolution using quantitative fluorescence microscopy. We conducted these experiments in anE. colistrain which is lacking all mechanosensitive channel genes save for MscL, whose expression was tuned across 3 orders of magnitude through modifications of the Shine-Dalgarno sequence. While theoretical models suggest that only a few MscL channels would be needed to alleviate even large changes in osmotic pressure, we find that between 500 and 700 channels per cell are needed to convey upwards of 80% survival. This number agrees with the average MscL copy number measured in wild-typeE. colicells through proteomic studies and quantitative Western blotting. Furthermore, we observed zero survival events in cells with fewer than ∼100 channels per cell. This work opens new questions concerning the contribution of other mechanosensitive channels to survival, as well as regulation of their activity.IMPORTANCEMechanosensitive (MS) channels are transmembrane protein complexes which open and close in response to changes in membrane tension as a result of osmotic shock. Despite extensive biophysical characterization, the contribution of these channels to cell survival remains largely unknown. In this work, we used quantitative video microscopy to measure the abundance of a single species of MS channel in single cells, followed by their survival after a large osmotic shock. We observed total death of the population with fewer than ∼100 channels per cell and determined that approximately 500 to 700 channels were needed for 80% survival. The number of channels we found to confer nearly full survival is consistent with the counts of the numbers of channels in wild-type cells in several earlier studies. These results prompt further studies to dissect the contribution of other channel species to survival.

scholarly journals The MscS and MscL Families of Mechanosensitive Channels Act as Microbial Emergency Release Valves

2012 ◽  
Vol 194 (18) ◽  
pp. 4802-4809 ◽  
Author(s):  
Ian R. Booth ◽  
Paul Blount
Keyword(s):  
Structure And Function ◽  
Mechanosensitive Channel ◽  
Protective Mechanism ◽  
Mechanosensitive Channels ◽  
Additional Pressure ◽  
Environmental Extremes ◽  
Life Threatening ◽  
And Function ◽  
Compare And Contrast ◽  
Plant Organelles

ABSTRACTSingle-celled organisms must survive exposure to environmental extremes. Perhaps one of the most variable and potentially life-threatening changes that can occur is that of a rapid and acute decrease in external osmolarity. This easily translates into several atmospheres of additional pressure that can build up within the cell. Without a protective mechanism against such pressures, the cell will lyse. Hence, most microbes appear to possess members of one or both families of bacterial mechanosensitive channels, MscS and MscL, which can act as biological emergency release valves that allow cytoplasmic solutes to be jettisoned rapidly from the cell. While this is undoubtedly a function of these proteins, the discovery of the presence of MscS homologues in plant organelles and MscL in fungus and mycoplasma genomes may complicate this simplistic interpretation of the physiology underlying these proteins. Here we compare and contrast these two mechanosensitive channel families, discuss their potential physiological roles, and review some of the most relevant data that underlie the current models for their structure and function.

scholarly journals Pocket delipidation induced by membrane tension or modification leads to a structurally analogous mechanosensitive channel state

Structure ◽  
2022 ◽  
Author(s):  
Bolin Wang ◽  
Benjamin J. Lane ◽  
Charalampos Kapsalis ◽  
James R. Ault ◽  
Frank Sobott ◽  
...  
Keyword(s):  
Mechanosensitive Channel ◽  
Membrane Tension ◽  
Channel State
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