Phase separation behavior of mixed lipid systems at neutral and low pH : coarse-grained simulations with DMD/LIME
We extend LIME, an intermediate resolution, implicit solvent model for phospholipids previously used in discontinuous molecular dynamics simulations of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer formation at 325 K, to the description of the geometry and energetics of 1,2-distearoyl-s...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1985. - 31(2015), 3 vom: 27. Jan., Seite 1086-94 |
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| Weitere Verfasser: | , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2015
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Lipid Bilayers Phosphatidylcholines Phosphoserine 17885-08-4 1,2-distearoyllecithin EAG959U971 |
| Zusammenfassung: | We extend LIME, an intermediate resolution, implicit solvent model for phospholipids previously used in discontinuous molecular dynamics simulations of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer formation at 325 K, to the description of the geometry and energetics of 1,2-distearoyl-sn-glycero-3-phospho-L-serine (DSPS) and 1,2-dihenarachidoyl-sn-glycero-3-phosphocholine (21PC) and mixtures thereof at both neutral and low pH at 310 K. A multiscale modeling approach is used to calculate the LIME parameters from atomistic simulation data on a mixed DPPC/DSPS system at different pH values. In the model, 17 coarse-grained sites represent DSPS and 18 coarse-grained sites represent 21PC. Each of these coarse-grained sites is classified as 1 of 9 types. LIME/DMD simulations of equimolar bilayers show the following: (1) 21PC/DSPS bilayers with and without surface area restrictions separate faster at low pH than at neutral pH, (2) 21PC/DSPS systems separate at approximately the same rate regardless of whether they are subjected to surface area restrictions, and (3) bilayers with a molar ratio of 9:1 (21PC:DSPS) phase separate to form heterogeneous domains faster at low pH than at neutral pH. Our results are consistent with experimental findings of Sofou and co-workers (Bandekar et al. Mol. Pharmaceutics, 2013, 10, 152-160; Karve et al. Biomaterials, 2010, 31, 4409-4416) that more doxorubicin is released from 21PC/DSPS liposomes at low pH than at neutral pH, presumably because greater phase separation is achieved at low pH than at neutral pH. These are the first molecular-level simulations of the phase separation in mixed lipid bilayers induced by a change in pH |
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| Beschreibung: | Date Completed 30.09.2015 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/la504082x |