Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS

Nomura, T; Cranfield, CG; Deplazes, E; Owen, DM; Macmillan, A; Battle, AR; Constantine, M; Sokabe, M; Martinac, B

Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS

Nomura, T Cranfield, CG

Deplazes, E

Owen, DM Macmillan, A Battle, AR Constantine, M Sokabe, M Martinac, B

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Publication Type:: Journal Article
Citation:: Proceedings of the National Academy of Sciences of the United States of America, 2012, 109 (22), pp. 8770 - 8775
Issue Date:: 2012-05-29

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Field	Value	Language
dc.contributor.author	Nomura, T	en_US
dc.contributor.author	Cranfield, CG https://orcid.org/0000-0003-3608-5440	en_US
dc.contributor.author	Deplazes, E https://orcid.org/0000-0003-2052-5536	en_US
dc.contributor.author	Owen, DM	en_US
dc.contributor.author	Macmillan, A	en_US
dc.contributor.author	Battle, AR	en_US
dc.contributor.author	Constantine, M	en_US
dc.contributor.author	Sokabe, M	en_US
dc.contributor.author	Martinac, B	en_US
dc.date.issued	2012-05-29	en_US
dc.identifier.citation	Proceedings of the National Academy of Sciences of the United States of America, 2012, 109 (22), pp. 8770 - 8775	en_US
dc.identifier.issn	0027-8424	en_US
dc.identifier.uri	http://hdl.handle.net/10453/29881
dc.description.abstract	Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are the major players in the protection of bacterial cells against hypoosmotic shock. Although a great deal is known about structure and function of these channels, much less is known about how membrane lipids may influence their mechanosensitivity and function. In this study, we use liposome coreconstitution to examine the effects of different types of lipids on MscS and MscL mechano-sensitivity simultaneously using the patch-clamp technique and confocal microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated that coreconstitution of MscS and MscL led to clustering of these channels causing a significant increase in the MscS activation threshold. Furthermore, the MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker bilayers and upon addition of cholesterol, known to affect the bilayer thickness, stiffness and pressure profile. In contrast, application of micromolar concentrations of lysophosphatidylcholine (LPC) led to an increase of the MscL/MscS threshold ratio. These data suggest that differences in hydrophobic mismatch and bilayer stiffness, change in transbilayer pressure profile, and close proximity of MscL and MscS affect the structural dynamics of both channels to a different extent. Our findings may have far-reaching implications for other types of ion channels and membrane proteins that, like MscL and MscS, may coexist in multiple molecular complexes and, consequently, have their activation characteristics significantly affected by changes in the lipid environment and their proximity to each other.	en_US
dc.relation.ispartof	Proceedings of the National Academy of Sciences of the United States of America	en_US
dc.relation.isbasedon	10.1073/pnas.1200051109	en_US
dc.subject.mesh	Spheroplasts	en_US
dc.subject.mesh	Escherichia coli	en_US
dc.subject.mesh	Lipids	en_US
dc.subject.mesh	Lipid Bilayers	en_US
dc.subject.mesh	Phosphatidylcholines	en_US
dc.subject.mesh	Lysophospholipids	en_US
dc.subject.mesh	Escherichia coli Proteins	en_US
dc.subject.mesh	Ion Channels	en_US
dc.subject.mesh	Liposomes	en_US
dc.subject.mesh	Microscopy, Confocal	en_US
dc.subject.mesh	Microscopy, Fluorescence	en_US
dc.subject.mesh	Fluorescence Resonance Energy Transfer	en_US
dc.subject.mesh	Patch-Clamp Techniques	en_US
dc.subject.mesh	Mechanotransduction, Cellular	en_US
dc.title	Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS	en_US
dc.type	Journal Article
utslib.citation.volume	22	en_US
utslib.citation.volume	109	en_US
utslib.for	0605 Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access
pubs.issue	22	en_US
pubs.publication-status	Published	en_US
pubs.volume	109	en_US

Abstract:

Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are the major players in the protection of bacterial cells against hypoosmotic shock. Although a great deal is known about structure and function of these channels, much less is known about how membrane lipids may influence their mechanosensitivity and function. In this study, we use liposome coreconstitution to examine the effects of different types of lipids on MscS and MscL mechano-sensitivity simultaneously using the patch-clamp technique and confocal microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated that coreconstitution of MscS and MscL led to clustering of these channels causing a significant increase in the MscS activation threshold. Furthermore, the MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker bilayers and upon addition of cholesterol, known to affect the bilayer thickness, stiffness and pressure profile. In contrast, application of micromolar concentrations of lysophosphatidylcholine (LPC) led to an increase of the MscL/MscS threshold ratio. These data suggest that differences in hydrophobic mismatch and bilayer stiffness, change in transbilayer pressure profile, and close proximity of MscL and MscS affect the structural dynamics of both channels to a different extent. Our findings may have far-reaching implications for other types of ion channels and membrane proteins that, like MscL and MscS, may coexist in multiple molecular complexes and, consequently, have their activation characteristics significantly affected by changes in the lipid environment and their proximity to each other.

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http://hdl.handle.net/10453/29881