Probing the association of triblock copolymers with supported lipid membranes using microcantilevers

Wang, Jinghui; Segatori, Laura; Biswal, Sibani Lisa

doi:10.1039/c4sm00928b

Cited by 23 publications

(43 citation statements)

References 64 publications

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“…Earlier work using lipid monolayers, unilamellar vesicles, or supported bilayers as model membrane systems has provided some physical insight into polymer-membrane association. 24,25,26,27,28,29 For example, it has been proposed that the hydrophobic PPO block favors insertion into the lipid tail region, whereas the hydrophilic PEO block may only weakly adsorb onto the lipid headgroups. 25 Small angle X-ray scattering (SAXS) experiments by Firestone et al further demonstrated that the length of the hydrophobic PPO block is a key determinant of the interaction mechanism with lipid bilayers.…”

Section: Introductionmentioning

confidence: 99%

“…33,34 A previous study of polymer interactions with supported lipid membranes using a microcantilever compared two Pluronics with the same PPO/PEO ratio but different molecular weight, and found that higher molecular weight enhances the association with lipid membranes. 29 Recently, on the basis of an in-vitro cellular assay it was found that the protection efficacy of PPO-PEO block copolymers on cell membranes is highly affected by the polymer composition as well as the overall molecular weight. 35 In this context, the polymer structure plays a critical role in the nature of the interactions between PPO-PEO block copolymers and lipid membranes, which therefore determines the performance of polymers in both membrane stabilization and permeabilization.…”

Section: Introductionmentioning

confidence: 99%

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Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers

et al. 2017

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Block copolymers composed of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) have been widely used in cell membrane stabilization and permeabilization. To explore the mechanism of interaction between PPO-PEO block copolymers and lipid membranes, we have investigated how polymer structure influences the polymer-lipid bilayer association by varying the overall molecular weight, the hydrophobic and hydrophilic block lengths, and the endgroup structure systematically, using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) unilamellar liposomes as model membranes. Pulsed-field-gradient NMR (PFG-NMR) was employed to probe polymer diffusion in the absence and presence of liposomes. The echo decay curves of free polymers in the absence of liposomes are single exponentials, indicative of simple translational diffusion, while in the presence of liposomes, the decays were biexponential, with the slower decay corresponding to polymers bound to liposomes. The binding percentage of polymer to the liposome was quantified by fitting the echo decay curves to a biexponential model. The NMR experiments showed that increasing the total molecular weight and hydrophobicity of the polymer can significantly enhance the polymer-lipid bilayer association, as the binding percentage and liposome surface coverage both increase. We hypothesize that the hydrophobic PPO block inserts into the lipid bilayer, due to the fact that little molecular exchange between bound and free polymers occurs on the time scale of the diffusion experiments. Additionally, as polymer concentration increases, the liposome surface coverage increases and approaches a limit. These results demonstrate that PFG-NMR is a simple yet powerful method to quantify interactions between polymers and lipid bilayers.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers

et al. 2017

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“…Similar results were obtained from molecular dynamics simulations 46,47 . At fixed PEO/PPO ratio, it was experimentally observed that increasing molecular weight enhanced interaction between the polymer and lipid, retarding the lipid diffusion in turn 48,49 . Conformations of the poloxamers interacting with lipid membranes have been studied by synchrotron X-ray scattering 50,51 and computational simulation 52 .…”

Section: Introductionmentioning

confidence: 99%

PEO–PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture

et al. 2017

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Poloxamer 188, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), protects cellular membranes from various stresses. Though numerous block copolymer variants exist, evaluation of alternative architecture, composition, and size has been minimal. Herein, cultured murine myoblasts are exposed to the stresses of hypotonic shock and isotonic recovery, and membrane integrity was evaluated by quantifying release of lactate dehydrogenase. Comparative evaluation of a systematic set of PEO-PPO diblock and PEO-PPO-PEO triblock copolymers demonstrates that the diblock architecture can be protective in vitro. Short PPO blocks hinder protection with >9 PPO units needed for protection at 150 µM and >16 units needed at 14 µM. Addition of a tert-butyl end group enhances protection at reduced concentration. When the end group and PPO length are fixed, increasing the PEO length improves protection. This systematic evaluation establishes a new in vitro screening tool for evaluating membrane-sealing amphiphiles and provides mechanistic insight to guide future copolymer design for membrane stabilization in vivo.

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“…In addition, temperature can play an important role on the solubility of the polymer in the membranes. 16 Experiments generally indicate that the interactions occur in two possible scenarios: (1) adsorption of polymer to the membrane surface, which is observed in all types of Pluronics, and (2) insertion of more hydrophobic polymers into the membrane. Although these observations appear consistent among experiments, a clear understanding of the mechanisms and driving forces that facilitate Pluronic−membrane interactions at atomic level remains elusive.…”

Section: ■ Introductionmentioning

confidence: 99%

“…To design effective nanomedicines, it is important to understand these interactions and the underlying molecular mechanisms in detail. Several experimental studies have been conducted in this context using different types of Pluronics, membrane models (monolayers, 14 bilayers, 15,16 liposomes, 9,17 and cells 18 ), and experimental methods including fluorescence microscopy, 14 X-ray scattering and differential scanning calorimetry, 15,17,19 dynamic nuclear polarization, 9 and microcantilever sensing. 16 Most of these studies indicate that the association of Pluronics with the lipid membranes depends on the length of the PPO block, hydrophilicity of the copolymer, membrane type, and membrane composition.…”

Section: ■ Introductionmentioning

confidence: 99%

Understanding the Interaction of Pluronics L61 and L64 with a DOPC Lipid Bilayer: An Atomistic Molecular Dynamics Study

et al. 2016

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ABSTRACT:We investigate the interactions of Pluronics L61 and L64 with a dioleylphosphatidylcholine (DOPC) lipid bilayer by atomistic molecular dynamics simulations using the all-atom OPLS force field. Our results show that the initial configuration of the polymer with respect to the bilayer determines its final conformation within the bilayer. When the polymer is initially placed at the lipid/water interface, we observe partial insertion of the polymer in a U-shaped conformation. On the other hand, when the polymer is centered at the bilayer, it stabilizes to a transmembrane state, which facilitates water transport across the bilayer. We show that membrane thickness decreases while its fluidity increases in the presence of Pluronics. When the polymer concentration inside the bilayer is high, pore formation is initiated with L64. Our results show good agreement with existing experimental data and reveal that the hydrophilic/lipophilic balance of the polymer plays a critical role in the interaction mechanisms as well as in the dynamics of Pluronics with and within the bilayer.

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Probing the association of triblock copolymers with supported lipid membranes using microcantilevers

Cited by 23 publications

References 64 publications

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers

Quantifying Binding of Ethylene Oxide–Propylene Oxide Block Copolymers with Lipid Bilayers

PEO–PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture

Understanding the Interaction of Pluronics L61 and L64 with a DOPC Lipid Bilayer: An Atomistic Molecular Dynamics Study

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