Effect of Bottlebrush Poloxamer Architecture on Binding to Liposomes.
Biomacromolecules
; 24(1): 449-461, 2023 01 09.
Article
em En
| MEDLINE
| ID: mdl-36563027
ABSTRACT
Poloxamersâtriblock copolymers consisting of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO)âhave demonstrated cell membrane stabilization efficacy against numerous types of stress. However, the mechanism responsible for this stabilizing effect remains elusive, hindering engineering of more effective therapeutics. Bottlebrush polymers have a wide parameter space and known relationships between architectural parameters and polymer properties, enabling their use as a tool for mechanistic investigations of polymer-lipid bilayer interactions. In this work, we utilized a versatile synthetic platform to create novel bottlebrush analogues to poloxamers and then employed pulsed-field-gradient NMR and an in vitro osmotic stress assay to explore the effect of bottlebrush architectural parameters on binding to, and protection of, model phospholipid bilayers. We found that the binding affinity of a bottlebrush poloxamer (BBP) (B-E1043P515, Mn ≈ 26 kDa) is about 3 times higher than a linear poloxamer with a similar composition and number of PPO units (L-E93P54E93, Mn ≈ 11 kDa). Furthermore, BBP binding is sensitive to overall molecular weight, side-chain length, and architecture (statistical versus block). Finally, all tested BBPs exhibit a protective effect on cell membranes under stress at sub-µM concentrations. As the factors controlling membrane affinity and protection efficacy of bottlebrush poloxamers are not understood, these results provide important insight into how they adhere to and stabilize a lipid bilayer surface.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Poloxâmero
/
Bicamadas Lipídicas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article