Nanoscale Membrane Domain Formation Driven by Cholesterol

Abstract Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via micros...

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Autores principales:	Matti Javanainen, Hector Martinez-Seara, Ilpo Vattulainen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6acfacbd7e0742ddbe49ca6ba326a7a4
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spelling	oai:doaj.org-article:6acfacbd7e0742ddbe49ca6ba326a7a42021-12-02T16:08:21ZNanoscale Membrane Domain Formation Driven by Cholesterol10.1038/s41598-017-01247-92045-2322https://doaj.org/article/6acfacbd7e0742ddbe49ca6ba326a7a42017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01247-9https://doaj.org/toc/2045-2322Abstract Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic experimental techniques due to their small size, yet there is also a lack of atomistic simulation models able to describe spontaneous nanodomain formation in sufficiently simple but biologically relevant complex membranes. Here we use atomistic simulations to consider a binary mixture of saturated dipalmitoylphosphatidylcholine and cholesterol — the “minimal standard” for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets. The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip–flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains. The model considered explains a plethora of controversial experimental results and provides an excellent basis for further computational studies on nanodomains. Furthermore, the results highlight the role of cholesterol as a key player in the modulation of nanodomains for membrane protein function.Matti JavanainenHector Martinez-SearaIlpo VattulainenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matti Javanainen Hector Martinez-Seara Ilpo Vattulainen Nanoscale Membrane Domain Formation Driven by Cholesterol
description	Abstract Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic experimental techniques due to their small size, yet there is also a lack of atomistic simulation models able to describe spontaneous nanodomain formation in sufficiently simple but biologically relevant complex membranes. Here we use atomistic simulations to consider a binary mixture of saturated dipalmitoylphosphatidylcholine and cholesterol — the “minimal standard” for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets. The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip–flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains. The model considered explains a plethora of controversial experimental results and provides an excellent basis for further computational studies on nanodomains. Furthermore, the results highlight the role of cholesterol as a key player in the modulation of nanodomains for membrane protein function.
format	article
author	Matti Javanainen Hector Martinez-Seara Ilpo Vattulainen
author_facet	Matti Javanainen Hector Martinez-Seara Ilpo Vattulainen
author_sort	Matti Javanainen
title	Nanoscale Membrane Domain Formation Driven by Cholesterol
title_short	Nanoscale Membrane Domain Formation Driven by Cholesterol
title_full	Nanoscale Membrane Domain Formation Driven by Cholesterol
title_fullStr	Nanoscale Membrane Domain Formation Driven by Cholesterol
title_full_unstemmed	Nanoscale Membrane Domain Formation Driven by Cholesterol
title_sort	nanoscale membrane domain formation driven by cholesterol
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6acfacbd7e0742ddbe49ca6ba326a7a4
work_keys_str_mv	AT mattijavanainen nanoscalemembranedomainformationdrivenbycholesterol AT hectormartinezseara nanoscalemembranedomainformationdrivenbycholesterol AT ilpovattulainen nanoscalemembranedomainformationdrivenbycholesterol
_version_	1718384534146252800

Nanoscale Membrane Domain Formation Driven by Cholesterol

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