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Molecular interactions of phospholipid monolayers with a model phospholipase

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Abstract

The intrinsic overexpression of secretory phospholipase A2 (sPLA2) in various pro-inflammatory diseases and cancers has the potential to be exploited as a therapeutic strategy for diagnostics and treatment. To explore this potential and advance our knowledge of the role of sPLA2 in related diseases, it is necessary to systematically investigate the molecular interaction of the enzyme with lipids. By employing a Langmuir trough integrated with X-ray reflectivity and grazing incidence X-ray diffraction techniques, this study examined the molecular packing structure of 1,2-palmitoyl-sn-glycero-3-phosphocholine (DPPC) films before and after enzyme adsorption and enzyme-catalyzed degradation. Molecular interaction of sPLA2 (from bee venom) with the DPPC monolayer exhibited Ca2+ dependence. DPPC molecules at the interface without Ca2+ retained a monolayer organization; upon adsorption of sPLA2 to the monolayer the packing became tighter. In contrast, sPLA2-catalyzed degradation of DPPC occurred in the presence of Ca2+, leading to disruption of the ordered monolayer structure of DPPC. The interfacial film became a mixture of highly ordered multilayer domains of palmitic acid (PA) and loosely packed monolayer phase of 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (lysoPC) that potentially contained the remaining un-degraded DPPC. The redistribution of lipid degradation products into the third dimension, which produced multilayer PA domains, damaged the structural integrity of the original lipid layer and may explain the bursting of liposomes observed in other studies after a latency period of mixing liposomes with sPLA2. A quantitative understanding of the lipid packing and lipid-enzyme interaction provides an intuitive means of designing and optimizing lipid-related drug delivery systems.

Graphical abstract: Molecular interactions of phospholipid monolayers with a model phospholipase

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Publication details

The article was received on 06 Jun 2018, accepted on 01 Apr 2019 and first published on 02 Apr 2019


Article type: Paper
DOI: 10.1039/C8SM01154K
Citation: Soft Matter, 2019, Advance Article

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    Molecular interactions of phospholipid monolayers with a model phospholipase

    P. Zhang, V. Villanueva, J. Kalkowski, C. Liu, A. J. Donovan, W. Bu, M. L. Schlossman, B. Lin and Y. Liu, Soft Matter, 2019, Advance Article , DOI: 10.1039/C8SM01154K

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