Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement

Holme, M, Rashid, M, Thomas, M, Barriga, H, Herpoldt, K, Heenan, R, Dreiss, C, Bañuelos, J, Xie, H, Yarovsky, I and Stevens, M 2018, 'Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement', ACS Central Science, vol. 4, no. 8, pp. 1023-1030.

Document type: Journal Article
Collection: Journal Articles

Title Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement
Author(s) Holme, M
Rashid, M
Thomas, M
Barriga, H
Herpoldt, K
Heenan, R
Dreiss, C
Bañuelos, J
Xie, H
Yarovsky, I
Stevens, M
Year 2018
Journal name ACS Central Science
Volume number 4
Issue number 8
Start page 1023
End page 1030
Total pages 8
Publisher American Chemical Society
Abstract Understanding the origins of lipid membrane bilayer rearrangement in response to external stimuli is an essential component of cell biology and the bottom-up design of liposomes for biomedical applications. The enzymes phospholipase C and D (PLC and PLD) both cleave the phosphorus-oxygen bonds of phosphate esters in phosphatidylcholine (PC) lipids. The atomic position of this hydrolysis reaction has huge implications for the stability of PC-containing self-assembled structures, such as the cell wall and lipid-based vesicle drug delivery vectors. While PLC converts PC to diacylglycerol (DAG), the interaction of PC with PLD produces phosphatidic acid (PA). Here we present a combination of small-angle scattering data and all-atom molecular dynamics simulations, providing insights into the effects of atomic-scale reorganization on the supramolecular assembly of PC membrane bilayers upon enzyme-mediated incorporation of DAG or PA. We observed that PC liposomes completely disintegrate in the presence of PLC, as conversion of PC to DAG progresses. At lower concentrations, DAG molecules within fluid PC bilayers form hydrogen bonds with backbone carbonyl oxygens in neighboring PC molecules and burrow into the hydrophobic region. This leads initially to membrane thinning followed by a swelling of the lamellar phase with increased DAG. At higher DAG concentrations, localized membrane tension causes a change in lipid phase from lamellar to the hexagonal and micellar cubic phases. Molecular dynamics simulations show that this destabilization is also caused in part by the decreased ability of DAG-containing PC membranes to coordinate sodium ions. Conversely, PLD-treated PC liposomes remain stable up to extremely high conversions to PA. Here, the negatively charged PA headgroup attracts significant amounts of sodium ions from the bulk solution to the membrane surface, leading to a swelling of the coordinated water layer. These findings are a vital step toward a fundamental underst
Subject Chemical Sciences not elsewhere classified
DOI - identifier 10.1021/acscentsci.8b00286
Copyright notice © 2018 American Chemical Society. Creative Commons Attribution (CC-BY) License
ISSN 2374-7951
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