Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes
We report all-atom molecular dynamics simulations of asymmetric bilayers containing phosphoinositides in the presence of monovalent and divalent cations. We have characterized the molecular mechanism by which these divalent cations interact with phosphoinositides. Ca2+ desolvates more readily, consi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2020-05-01
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| Series: | Royal Society Open Science |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.192208 |
| _version_ | 1818405640721137664 |
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| author | Ryan P. Bradley David R. Slochower Paul A. Janmey Ravi Radhakrishnan |
| author_facet | Ryan P. Bradley David R. Slochower Paul A. Janmey Ravi Radhakrishnan |
| author_sort | Ryan P. Bradley |
| collection | DOAJ |
| description | We report all-atom molecular dynamics simulations of asymmetric bilayers containing phosphoinositides in the presence of monovalent and divalent cations. We have characterized the molecular mechanism by which these divalent cations interact with phosphoinositides. Ca2+ desolvates more readily, consistent with single-molecule calculations, and forms a network of ionic-like bonds that serve as a ‘molecular glue’ that allows a single ion to coordinate with up to three phosphatidylinositol-(4,5)-bisphosphate (PI(4, 5)P2) lipids. The phosphatidylinositol-(3,5)-bisphosphate isomer shows no such effect and neither does PI(4, 5)P2 in the presence of Mg2+. The resulting network of Ca2+-mediated lipid-lipid bonds grows to span the entire simulation space and therefore has implications for the lateral distribution of phosophoinositides in the bilayer. We observe context-specific differences in lipid diffusion rates, lipid surface densities and bilayer structure. The molecular-scale delineation of ion-lipid arrangements reported here provides insight into similar nanocluster formation induced by peripheral proteins to regulate the formation of functional signalling complexes on the membrane. |
| first_indexed | 2024-12-14T08:59:16Z |
| format | Article |
| id | doaj.art-e6956f8bdb2847a7be8d643af43954e1 |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-12-14T08:59:16Z |
| publishDate | 2020-05-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-e6956f8bdb2847a7be8d643af43954e12022-12-21T23:08:51ZengThe Royal SocietyRoyal Society Open Science2054-57032020-05-017510.1098/rsos.192208192208Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranesRyan P. BradleyDavid R. SlochowerPaul A. JanmeyRavi RadhakrishnanWe report all-atom molecular dynamics simulations of asymmetric bilayers containing phosphoinositides in the presence of monovalent and divalent cations. We have characterized the molecular mechanism by which these divalent cations interact with phosphoinositides. Ca2+ desolvates more readily, consistent with single-molecule calculations, and forms a network of ionic-like bonds that serve as a ‘molecular glue’ that allows a single ion to coordinate with up to three phosphatidylinositol-(4,5)-bisphosphate (PI(4, 5)P2) lipids. The phosphatidylinositol-(3,5)-bisphosphate isomer shows no such effect and neither does PI(4, 5)P2 in the presence of Mg2+. The resulting network of Ca2+-mediated lipid-lipid bonds grows to span the entire simulation space and therefore has implications for the lateral distribution of phosophoinositides in the bilayer. We observe context-specific differences in lipid diffusion rates, lipid surface densities and bilayer structure. The molecular-scale delineation of ion-lipid arrangements reported here provides insight into similar nanocluster formation induced by peripheral proteins to regulate the formation of functional signalling complexes on the membrane.https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.192208molecular dynamicsasymmetric bilayerphosphoinositides |
| spellingShingle | Ryan P. Bradley David R. Slochower Paul A. Janmey Ravi Radhakrishnan Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes Royal Society Open Science molecular dynamics asymmetric bilayer phosphoinositides |
| title | Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes |
| title_full | Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes |
| title_fullStr | Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes |
| title_full_unstemmed | Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes |
| title_short | Divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano-cluster initiation in bilayer membranes |
| title_sort | divalent cations bind to phosphoinositides to induce ion and isomer specific propensities for nano cluster initiation in bilayer membranes |
| topic | molecular dynamics asymmetric bilayer phosphoinositides |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.192208 |
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