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

ACS Central Science
Margaret N HolmeMolly M Stevens

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 le...Continue Reading

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Citations

Mar 15, 2019·The Journal of Pharmacology and Experimental Therapeutics·Xing XuYu Liu
Mar 17, 2021·Biochimica Et Biophysica Acta. Biomembranes·Nejc PetrišičGregor Anderluh
May 25, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Apratim JashSyed S H Rizvi
Apr 13, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Valeria NeleMolly M Stevens
Oct 24, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Wye-Khay FongRaffaele Mezzenga
Sep 29, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Valeria NeleMolly M Stevens

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Methods Mentioned

BETA
small-angle
X-ray
SANS
Neutron
dynamic light scattering
small-angle scattering

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