Cholesterol Flip-Flop in Heterogeneous Membranes
Cholesterol is the most abundant molecule in the plasma membrane of mammals. Its distribution across the two membrane leaflets is critical for understanding how cells work. Cholesterol trans-bilayer motion (flip-flop) is a key process influencing its distribution in membranes. Despite extensive inve...
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Veröffentlicht in: | Journal of chemical theory and computation 2019-03, Vol.15 (3), p.2064-2070 |
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creator | Gu, Ruo-Xu Baoukina, Svetlana Tieleman, D. Peter |
description | Cholesterol is the most abundant molecule in the plasma membrane of mammals. Its distribution across the two membrane leaflets is critical for understanding how cells work. Cholesterol trans-bilayer motion (flip-flop) is a key process influencing its distribution in membranes. Despite extensive investigations, the rate of cholesterol flip-flop and its dependence on the lateral heterogeneity of membranes remain uncertain. In this work, we used atomistic molecular dynamics simulations to sample spontaneous cholesterol flip-flop events in a DPPC:DOPC:cholesterol mixture with heterogeneous lateral distribution of lipids. In addition to an overall flip-flop rate at the time scale of sub-milliseconds, we identified a significant impact of local environment on flip-flop rate. We discuss the atomistic details of the flip-flop events observed in our simulations. |
doi_str_mv | 10.1021/acs.jctc.8b00933 |
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Peter</creator><creatorcontrib>Gu, Ruo-Xu ; Baoukina, Svetlana ; Tieleman, D. Peter</creatorcontrib><description>Cholesterol is the most abundant molecule in the plasma membrane of mammals. Its distribution across the two membrane leaflets is critical for understanding how cells work. Cholesterol trans-bilayer motion (flip-flop) is a key process influencing its distribution in membranes. Despite extensive investigations, the rate of cholesterol flip-flop and its dependence on the lateral heterogeneity of membranes remain uncertain. In this work, we used atomistic molecular dynamics simulations to sample spontaneous cholesterol flip-flop events in a DPPC:DOPC:cholesterol mixture with heterogeneous lateral distribution of lipids. In addition to an overall flip-flop rate at the time scale of sub-milliseconds, we identified a significant impact of local environment on flip-flop rate. We discuss the atomistic details of the flip-flop events observed in our simulations.</description><identifier>ISSN: 1549-9618</identifier><identifier>EISSN: 1549-9626</identifier><identifier>DOI: 10.1021/acs.jctc.8b00933</identifier><identifier>PMID: 30633868</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Cholesterol ; Dependence ; Environmental impact ; Lipids ; Membranes ; Molecular dynamics</subject><ispartof>Journal of chemical theory and computation, 2019-03, Vol.15 (3), p.2064-2070</ispartof><rights>Copyright American Chemical Society Mar 12, 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a406t-9650d9102eb9ce098dfba3c5236acd651ab7177f860f3b1c77fdf154297f897d3</citedby><cites>FETCH-LOGICAL-a406t-9650d9102eb9ce098dfba3c5236acd651ab7177f860f3b1c77fdf154297f897d3</cites><orcidid>0000-0001-5507-0688 ; 0000-0003-2587-0232</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jctc.8b00933$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jctc.8b00933$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2764,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30633868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gu, Ruo-Xu</creatorcontrib><creatorcontrib>Baoukina, Svetlana</creatorcontrib><creatorcontrib>Tieleman, D. Peter</creatorcontrib><title>Cholesterol Flip-Flop in Heterogeneous Membranes</title><title>Journal of chemical theory and computation</title><addtitle>J. Chem. Theory Comput</addtitle><description>Cholesterol is the most abundant molecule in the plasma membrane of mammals. Its distribution across the two membrane leaflets is critical for understanding how cells work. Cholesterol trans-bilayer motion (flip-flop) is a key process influencing its distribution in membranes. Despite extensive investigations, the rate of cholesterol flip-flop and its dependence on the lateral heterogeneity of membranes remain uncertain. In this work, we used atomistic molecular dynamics simulations to sample spontaneous cholesterol flip-flop events in a DPPC:DOPC:cholesterol mixture with heterogeneous lateral distribution of lipids. In addition to an overall flip-flop rate at the time scale of sub-milliseconds, we identified a significant impact of local environment on flip-flop rate. We discuss the atomistic details of the flip-flop events observed in our simulations.</description><subject>Cholesterol</subject><subject>Dependence</subject><subject>Environmental impact</subject><subject>Lipids</subject><subject>Membranes</subject><subject>Molecular dynamics</subject><issn>1549-9618</issn><issn>1549-9626</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kL1PwzAQxS0EoqWwM6FILAyknO3EsUdUUYpUxAKzZTsOpHI-sJuB_x73c0BiutPp9949PYSuMUwxEPygTJiuzNpMuQYQlJ6gMc4zkQpG2Olxx3yELkJYAVCaEXqORhQYpZzxMYLZV-dsWFvfuWTu6j6du65P6jZZ2M3x07a2G0LyahvtVWvDJTqrlAv2aj8n6GP-9D5bpMu355fZ4zJVGbB1_JpDKWJIq4WxIHhZaUVNTihTpmQ5VrrARVFxBhXV2MS1rGJeIuJNFCWdoLudb--77yEmlE0djHVObQNJggtBo0-GI3r7B111g29jOkkIiJyDKHikYEcZ34XgbSV7XzfK_0gMctOmjG3KTZty32aU3OyNB93Y8ig41BeB-x2wlR6e_uv3C-myfsM</recordid><startdate>20190312</startdate><enddate>20190312</enddate><creator>Gu, Ruo-Xu</creator><creator>Baoukina, Svetlana</creator><creator>Tieleman, D. Peter</creator><general>American Chemical Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SC</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>JQ2</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5507-0688</orcidid><orcidid>https://orcid.org/0000-0003-2587-0232</orcidid></search><sort><creationdate>20190312</creationdate><title>Cholesterol Flip-Flop in Heterogeneous Membranes</title><author>Gu, Ruo-Xu ; Baoukina, Svetlana ; Tieleman, D. 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subjects | Cholesterol Dependence Environmental impact Lipids Membranes Molecular dynamics |
title | Cholesterol Flip-Flop in Heterogeneous Membranes |
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