Influence of Cholesterol and Bilayer Curvature on the Interaction of PPO-PEO Block Copolymers with Liposomes

Interactions of nonionic poly(ethylene oxide)- b-poly(propylene oxide) (PEO-PPO) block copolymers, known as Pluronics or poloxamers, with cell membranes have been widely studied for a host of biomedical applications. Herein, we report how cholesterol within phosphatidylcholine (POPC) lipid bilayer l...

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Publié dans:Langmuir : the ACS journal of surfaces and colloids. - 1985. - 35(2019), 22 vom: 04. Juni, Seite 7231-7241
Auteur principal: Zhang, Wenjia (Auteur)
Autres auteurs: Coughlin, McKenzie L, Metzger, Joseph M, Hackel, Benjamin J, Bates, Frank S, Lodge, Timothy P
Format: Article en ligne
Langue:English
Publié: 2019
Accès à la collection:Langmuir : the ACS journal of surfaces and colloids
Sujets:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Lipid Bilayers Phosphatidylcholines Polymers Propylene Glycols polypropylene glycol 25322-69-4 plus... Cholesterol 97C5T2UQ7J
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Résumé:Interactions of nonionic poly(ethylene oxide)- b-poly(propylene oxide) (PEO-PPO) block copolymers, known as Pluronics or poloxamers, with cell membranes have been widely studied for a host of biomedical applications. Herein, we report how cholesterol within phosphatidylcholine (POPC) lipid bilayer liposomes and bilayer curvature affects the binding of several PPO-PEO-PPO triblocks with varying PPO content and a tPPO-PEO diblock, where t refers to a tert-butyl end group. Pulsed-field-gradient NMR was employed to quantify the extent of copolymer associated with liposomes prepared with cholesterol concentrations ranging from 0 to 30 mol % relative to the total content of POPC and cholesterol and vesicle extrusion radii of 25, 50, or 100 nm. The fraction of polymer bound to the liposomes was extracted from NMR data on the basis of the very different mobilities of the bound and free polymers in aqueous solution. Cholesterol concentration was manipulated by varying the molar percentage of this sterol in the POPC bilayer preparation. The membrane curvature was varied by adjusting the liposome size through a conventional pore extrusion technique. Although the PPO content significantly influences the overall amount of block copolymer adsorbed to the liposome, we found that polymer binding decreases with increasing cholesterol concentration in a universal fashion, with the fraction of bound polymer dropping 10-fold between 0 and 30 mol % cholesterol relative to the total content of POPC and cholesterol. Increasing the bilayer curvature (decreasing the radius of the liposome) in the absence of cholesterol increases polymer binding between 2- and 4-fold over the range of liposome sizes studied. These results demonstrate that cholesterol plays a dominant role, and bilayer curvature has a less significant impact as the curvature decreases, on polymer-membrane association
Description:Date Completed 17.08.2020
Date Revised 28.03.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1520-5827
DOI:10.1021/acs.langmuir.9b00572