Cholesterol affected dynamics of lipids in tailor-made vesicles by ArcVes software during multi micro second coarse grained molecular dynamics simulations

Chia-Wen Wang; Meng-Han Lin; Wolfgang B. Fischer; Chia-Wen Wang; Meng-Han Lin; Wolfgang B. Fischer

doi:10.3934/biophy.2023027

AIMS Biophysics

2023, Volume 10, Issue 4: 482-502. doi: 10.3934/biophy.2023027

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Research article

Cholesterol affected dynamics of lipids in tailor-made vesicles by ArcVes software during multi micro second coarse grained molecular dynamics simulations

Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan

Received: 12 August 2023 Revised: 22 October 2023 Accepted: 01 November 2023 Published: 30 November 2023

In biotechnology, as well as in nanomedicine, vesicular structures are essential features of the cellular life cycle. Lipid compositions define the applicability of the vesicles. Here, the dynamics of lipid molecules within vesicles of approximately 10 nm in diameter are monitored using coarse-grained molecular dynamics (CGMD) simulations (MARTINI). The vesicles consist of (i) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), each in a mixture with cholesterol (CHOL) (POPC/CHOL, DOPC/CHOL), (ii) POPC/DOPC mixture and (iii) pure POPC and DOPC. Vesicles are generated by placing the individual lipids spatially separated by an area-per-lipid based distance onto the sphere using an arc correction, implemented into ArcVes, which is an in-house developed software. This protocol leads to the generation of vesicles which remain stable during extended MD simulations. In the presence of cholesterol, the mixed vesicles show time-dependent changes such as a decrease in both radii and membrane thickness. The number of lipids in each leaflet of the mixed vesicles reveals a trend of POPC and DOPC flipping to the outer leaflet and of cholesterol to the inner leaflet. This leads to a cholesterol rich path-formation in both the inner and outer leaflets. The diffusivity of the lipids in the vesicles mixed with cholesterol is lower than the diffusivity of the pure vesicles, similar to the observation for the respective flat membrane patches. In general, the diffusivity of the lipids is larger in the outer leaflets than the inner leaflets.
- vesicles,
- lipid membranes,
- lipid mixtures,
- cholesterol,
- aggregation,
- coarse-grained molecular dynamics simulations
Citation: Chia-Wen Wang, Meng-Han Lin, Wolfgang B. Fischer. Cholesterol affected dynamics of lipids in tailor-made vesicles by ArcVes software during multi micro second coarse grained molecular dynamics simulations[J]. AIMS Biophysics, 2023, 10(4): 482-502. doi: 10.3934/biophy.2023027

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Abstract

In biotechnology, as well as in nanomedicine, vesicular structures are essential features of the cellular life cycle. Lipid compositions define the applicability of the vesicles. Here, the dynamics of lipid molecules within vesicles of approximately 10 nm in diameter are monitored using coarse-grained molecular dynamics (CGMD) simulations (MARTINI). The vesicles consist of (i) 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), each in a mixture with cholesterol (CHOL) (POPC/CHOL, DOPC/CHOL), (ii) POPC/DOPC mixture and (iii) pure POPC and DOPC. Vesicles are generated by placing the individual lipids spatially separated by an area-per-lipid based distance onto the sphere using an arc correction, implemented into ArcVes, which is an in-house developed software. This protocol leads to the generation of vesicles which remain stable during extended MD simulations. In the presence of cholesterol, the mixed vesicles show time-dependent changes such as a decrease in both radii and membrane thickness. The number of lipids in each leaflet of the mixed vesicles reveals a trend of POPC and DOPC flipping to the outer leaflet and of cholesterol to the inner leaflet. This leads to a cholesterol rich path-formation in both the inner and outer leaflets. The diffusivity of the lipids in the vesicles mixed with cholesterol is lower than the diffusivity of the pure vesicles, similar to the observation for the respective flat membrane patches. In general, the diffusivity of the lipids is larger in the outer leaflets than the inner leaflets.

Acknowledgments

WBF thanks the Ministry of Science and Technology Taiwan (MOST-107-2112-M-010-002-MY3 and MOST-110-2112-M-A49A501) for financial support.

Conflict of interest

The authors declare no conflict of interest.

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