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

Wenjia Zhang, McKenzie L. Coughlin, Joseph M Metzger, Benjamin J Hackel, Frank S. Bates, Timothy P Lodge

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10 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7231-7241
Number of pages11
Issue number22
StatePublished - Jun 4 2019

Bibliographical note

Funding Information:
We acknowledge Karen J. Haman for synthesizing the diblock polymer and Mihee Kim for useful discussions. We also acknowledge Letitia J. Yao for help with the NMR experiments. NMR instrumentation was supported by the Office of the Vice President of Research, College of Science and Engineering, and the Department of Chemistry at the University of Minnesota. The cryo-TEM images were recorded in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program under Award Number DMR-1420013. This study was funded by the National Institutes of Health (grant R01HL122323).

How much support was provided by MRSEC?

  • Shared

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't


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