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The Impact of Lipid Digestion on the Dynamic and Structural Properties of Micelles

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number2004761
JournalSmall
Volume17
Issue number6
DOIs
Accepted/In press2021
Published11 Feb 2021

Bibliographical note

Funding Information: Via the membership of the UK's HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202, EP/R029431), this work used the ARCHER UK National Supercomputing Service (http://www.archer.ac.uk) and the UK Materials and Molecular Modeling Hub (MMM Hub) for computational resources, which is partially funded by EPSRC (EP/P020194/1) to carry out the MD simulations reported in this manuscript. The authors acknowledge the support by the Biotechnology and Biological Sciences Research Council (BB/M009513/1) via the London Interdisciplinary Doctoral Programme (LIDo). The authors thank Dr. Luke Clifton for the use of his program BSLDC (Biomolecular Scattering Length Density Calculator), available at http://psldc.isis.rl.ac.uk/Psldc/. Experiments at the ISIS Neutron and Muon Source were supported by beamtime allocation from STFC RB1010543 (Changes of phospholipid aggregate morphology induced by phospholipase hydrolysis). This work benefited from the use of the SasView application, originally developed under National Science Foundation Award DMR-0520547. SasView also contains a code developed with funding from the European Union's Horizon 2020 research and innovation program under the SINE2020 project, Grant No.?654000. Funding Information: Via the membership of the UK's HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202, EP/R029431), this work used the ARCHER UK National Supercomputing Service ( http://www.archer.ac.uk ) and the UK Materials and Molecular Modeling Hub (MMM Hub) for computational resources, which is partially funded by EPSRC (EP/P020194/1) to carry out the MD simulations reported in this manuscript. The authors acknowledge the support by the Biotechnology and Biological Sciences Research Council (BB/M009513/1) via the London Interdisciplinary Doctoral Programme (LIDo). The authors thank Dr. Luke Clifton for the use of his program BSLDC (Biomolecular Scattering Length Density Calculator), available at http://psldc.isis.rl.ac.uk/Psldc/ . Experiments at the ISIS Neutron and Muon Source were supported by beamtime allocation from STFC RB1010543 (Changes of phospholipid aggregate morphology induced by phospholipase hydrolysis). This work benefited from the use of the SasView application, originally developed under National Science Foundation Award DMR‐0520547. SasView also contains a code developed with funding from the European Union's Horizon 2020 research and innovation program under the SINE2020 project, Grant No. 654000. Publisher Copyright: © 2021 The Authors. Small published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Self-assembled, lipid-based micelles, such as those formed by the short-chain phosphocholine, dihexanoylphosphatidylcholine (2C6PC), are degraded by the pancreatic enzyme, phospholipase A2 (PLA2). Degradation yields 1-hexanoyl-lysophosphocholine (C6LYSO) and hexanoic acid (C6FA) products. However, little is known about the behavior of these products during and after the degradation of 2C6PC. In this work, a combination of static and time-resolved small angle neutron scattering, as well as all-atom molecular dynamics simulations, is used to characterize the structure of 2C6PC micelles. In doing so a detailed understanding of the substrate and product aggregation behavior before, during and after degradation is gained. Consequently, the formation of mixed micelles containing 2C6PC, C6LYSO and C6FA is shown at every stage of the degradation process, as well as the formation of mixed C6LYSO/C6FA micelles after degradation is complete. The use of atomistic molecular dynamics has allowed us to characterize the structure of 2C6PC, 2C6PC/C6LYSO/C6FA, and C6LYSO/C6FA micelles throughout the degradation process, showing the localization of the different molecular species within the aggregates. In addition, the hydration of the 2C6PC, C6LYSO, and C6FA species both during micellization and as monomers in aqueous solution is documented to reveal the processes driving their micellization.

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