Bilayer-Mediated Clustering and Functional Interaction of MscL Channels

Grage, Stephan L.; Keleshian, A.M.; Turdzeladze, Tamta; Battle, Andrew R.; Tay, Wee C.; May, Roland P.; Holt, Stephen A.; Contera, Sonia; Haertlein, Michael; Moulin, Martine; Pal, Prithwish; Rohde, Paul R.; Forsyth, V. Trevor; Watts, Anthony; Huang, Kerwyn Casey; Ulrich, Anne S.; Martinac, Boris

doi:10.1016/j.bpj.2011.01.023

Cited by 92 publications

(141 citation statements)

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“…These numbers take the channel density close to or above the threshold for cluster formation at low tensions. Patch-clamp experiments complemented with fluorescent and atomic force microscopy show evidence for crowding and collective response of channels in liposomes [31]. Other studies have shown non-homogeneous distributions of overexpressed MS channels in live bacterial cells [29,32,33].…”

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confidence: 89%

Cooperative response and clustering: Consequences of membrane-mediated interactions among mechanosensitive channels

2017

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Mechanosensitive (MS) channels are ion channels which act as cells' safety valves, opening when the osmotic pressure becomes too high and making cells avoid damage by releasing ions. They are found on the cellular membrane of a large number of organisms. They interact with each other by means of deformations they induce in the membrane. We show that collective dynamics arising from the inter-channel interactions lead to first and second-order phase transitions in the fraction of open channels in equilibrium relating to the formation of channel clusters. We show that this results in a considerable delay of the response of cells to osmotic shocks, and to an extreme cell-to-cell stochastic variations in their response times, despite the large numbers of channels present in each cell. We discuss how our results are relevant for E. coli.Abrupt changes in the osmolarity of the environment is a hazard most organisms are subject to at one time or another [1][2][3][4][5][6]. A sudden drop in osmolarity (an osmotic shock ) will cause water to rush into a living cell, and requires an immediate response by the cell to prevent it from getting damaged or undergoing lysis from the increased tension on the cellular membrane. Mechanosensitive channels (or MS channels) are ion channels located on the cell membrane, which open when the membrane tension becomes too high [7,8], and play a crucial role in the cell's defence mechanism against osmotic shocks [9,10]. They act as safety valves, releasing ions and decreasing the osmotic pressure and the membrane tension. Mechanosensitive channels are found in many organisms, and have been well characterised in the bacterium E. coli [11-13].The cellular membrane in which the mechanosensitive channels are inserted is a lipid bilayer. The interior of the bilayer is hydrophobic, making it energetically favourable for it to thicken or compress to match the hydrophobic parts of the channel proteins inserted in the membrane [14]. This results in a deformation profile around each channel, with the thickness of the bilayer being a function of position. This deformation mediates a shortrange effective force between two neighbouring channels, similar to the force between two nearby corks floating on water, which interact through the deformation they induce on the surface of water. This interaction can be attractive or repulsive, depending on the shapes of the two molecules. Furthermore, a theoretical analysis suggests that the interaction between two neighbouring channels lowers the tension needed to open them during an osmotic shock [15], raising the possibility that their function could be influenced by their spatial distribution on the membrane (as already noticed for other membrane proteins [16,17]). This is reinforced by the fact that the channels' attractive forces suggest that they may agglomerate into clusters. Our goal in this paper is to determine the consequences that the inter-channel interaction has on the dynamics of this system, focusing in particular on channel clustering and its con...

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confidence: 89%

Cooperative response and clustering: Consequences of membrane-mediated interactions among mechanosensitive channels

2017

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“…The channel activates in response to changes in membrane tension without the aid of other components and is highly stable, as shown in the conservation of its gating functionality after purification and reconstitution into lipid vesicles (58). Reconstitution of MscL can be carried out using a variety of different lipids (50), and the channel is readily engineered (77) with the inclusion of gain-and-loss-of-function mutants. These characteristics highlight the aptitude of MscL for use as a nanovalve in liposomal drug delivery systems.…”

Section: Mechanosensitive Channelsmentioning

confidence: 99%

Bacterial Mechanosensitive Channels: Models for Studying Mechanosensory Transduction

Martinac

Nomura

Chi

et al. 2014

Antioxidants & Redox Signaling

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Significance: Sensations of touch and hearing are manifestations of mechanical contact and air pressure acting on touch receptors and hair cells of the inner ear, respectively. In bacteria, osmotic pressure exerts a significant mechanical force on their cellular membrane. Bacteria have evolved mechanosensitive (MS) channels to cope with excessive turgor pressure resulting from a hypo-osmotic shock. MS channel opening allows the expulsion of osmolytes and water, thereby restoring normal cellular turgor and preventing cell lysis. Recent Advances: As biological force-sensing systems, MS channels have been identified as the best examples of membrane proteins coupling molecular dynamics to cellular mechanics. The bacterial MS channel of large conductance (MscL) and MS channel of small conductance (MscS) have been subjected to extensive biophysical, biochemical, genetic, and structural analyses. These studies have established MscL and MscS as model systems for mechanosensory transduction. Critical Issues: In recent years, MS ion channels in mammalian cells have moved into focus of mechanotransduction research, accompanied by an increased awareness of the role they may play in the pathophysiology of diseases, including cardiac hypertrophy, muscular dystrophy, or Xerocytosis. Future Directions: A recent exciting development includes the molecular identification of Piezo proteins, which function as nonselective cation channels in mechanosensory transduction associated with senses of touch and pain. Since research on Piezo channels is very young, applying lessons learned from studies of bacterial MS channels to establishing the mechanism by which the Piezo channels are mechanically activated remains one of the future challenges toward a better understanding of the role that MS channels play in mechanobiology. Antioxid. Redox Signal. 00, 000-000.

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“…The organization in nano-domains had been suspected for long, but a variety of super-resolution light microscopy techniques and atomic-force microscopy (AFM) have recently improved further our understanding of membrane supramolecular organization. They gave definitive evidence of the generic existence of nanometer sized functional domains on the cell membrane [2,4,5,6,7,8,9,10].…”

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confidence: 99%

“…E-cadherins constitute another example for which nano-patterning of the membrane has been shown to be involved in its biological function, clusters serving as adhesive foci in adherens junctions [14,15]. Grouping identical receptors in a same cluster can also optimize and make more reliable their response to external stimuli [6,8,16,17,19]. Clusters could also result in the inactivation or storage of proteins that would otherwise interact with their environment in a possibly unfavorable way.…”

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confidence: 99%

“…In order for the proteins to be condensed in a cluster phase, a generic attractive interaction at short range is required, the origin of which has been discussed in many works ( [6,10] and references therein). Two types of theoretical approaches have been developed to account for the finite size of protein clusters : (1) an effective long range repulsive potential between the proteins that prevents the creation of one big macrophase at equilibrium [18,19,21,22] and (2) far-from-equilibrium recycling of the cell membrane due to material exchange with the cytosol, that continually mixes the plasma membrane components and breaks large assemblies [23,24,25,26].…”

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confidence: 99%

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Nanodomains in Biomembranes with Recycling

2016

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Cell membranes are out of thermodynamic equilibrium notably because of membrane recycling, i.e. active exchange of material with the cytosol. We propose an analytically tractable model of biomembrane predicting the effects of recycling on the size of protein nanodomains. It includes a short-range attraction between proteins and a weaker long-range repulsion which ensures the existence of socalled cluster phases at equilibrium, where monomeric proteins coexist with finite-size domains. Our main finding is that when taking recycling into account, the typical cluster size increases logarithmically with the recycling rate. Using physically realistic model parameters, the predicted two-fold increase due to recycling in living cells is very likely experimentally measurable with the help of superresolution microscopy.

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Bilayer-Mediated Clustering and Functional Interaction of MscL Channels

Cited by 92 publications

References 37 publications

Cooperative response and clustering: Consequences of membrane-mediated interactions among mechanosensitive channels

Cooperative response and clustering: Consequences of membrane-mediated interactions among mechanosensitive channels

Bacterial Mechanosensitive Channels: Models for Studying Mechanosensory Transduction

Nanodomains in Biomembranes with Recycling

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