Styrene maleic acid copolymer induces pores in biomembranes

Rydmark, Marcella Orwick; Christensen, Marianne; Köksal, Elif Senem; Kantarci, Ilayda; Kustanovich, Kiryl; Yantchev, Ventsislav; Jesorka, Aldo; Gözen, İrep

doi:10.1039/c9sm01407a

Cited by 16 publications

(23 citation statements)

References 33 publications

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“…The generation of morphologically and pathologically distinct amylin species reported here by lipid solubilizing SMA copolymers [46][47][48] could be useful in strategically designing amyloid inhibitors that could potentially be useful to suppress IAPP induced cell toxicity in type-2 diabetes.…”

Section: Discussionmentioning

confidence: 96%

“…On the other hand, the reported results can be used to develop further experimental strategies to solve atomic-resolution structures of amylin intermediates to better understand the correlation between structure and toxicity of amylin species. The generation of morphologically and pathologically distinct amylin species reported here by lipid solubilizing SMA copolymers[46–48] could be useful in strategically designing amyloid inhibitors that could potentially be useful to suppress IAPP induced cell toxicity in type-2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, this study delineates the effects of SMA copolymers that are capable of solubilizing lipids and penetrating the cell membrane. [35][36][37][38][39] The charge and hydrophobic interaction mediated generation of morphologically distinct amylin species reported here could be useful in designing strategic amyloid inhibitors. In vitro and in vivo results showed SMAEA and SMAQA polymers were not toxic to kidney HEK293T cells and zebrafish embryo ( Figure S21).…”

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confidence: 99%

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Conformational Tuning of Amylin by Charged Styrene-maleic-acid Copolymers

Sahoo¹,

Souders²,

Ivanova³

et al. 2020

Preprint

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Human amylin is linked to type-2 diabetes and forms structurally heterogeneous amyloids that are pathologically relevant. Therefore, understanding the fundamental forces governing the formation of heterogeneous aggregates is important. Here, using derivatives (SMAQA + /SMAEA -) of styrene-maleic-acid (SMA) copolymer (~2.2kDa), we demonstrate the quick formation (~ in minutes) of amylin globulomers and fibers. High-speed AFM tracked the quick formation of de novo globular amylin oligomers and arrestment of fibrillation by SMAQA, whereas SMAEA accelerates amylin fibrillation. This observation is further supported by DOSY and STD NMR experiments. CD results show that SMAQA or SMAEA binding generates α-helix or β-sheet rich amylin structures, respectively. Atomistic insights are revealed by 2D NMR and microseconds all-atom MD simulation. Together, this study highlights the importance of charge-charge interaction in tuning the fibrillation pathways of amylin that could be of therapeutic interest.Supporting information for this article is given via a link at the end of the document

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Conformational Tuning of Amylin by Charged Styrene-maleic-acid Copolymers

Sahoo¹,

Souders²,

Ivanova³

et al. 2020

Preprint

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“…While surrounding the lipid bilayer, interestingly, SMA polymer is more stretched (showing higher gyration radius) than free polymers in solution [ 50 ]. On the other hand, the encapsulation event perturbs the membrane curvature (by forming a bulge) and planarity, and allows formation of toroidal pores [ 56 ] so that water and water-soluble molecules such as fluorescein can permeate inside ( Figure 6 A) Intriguingly, after encapsulation, the distribution of Na+ ions undergo remarkable changes, as well, and that compensates the repulsion between anionic carboxyl moieties in the lipid-water interface. Small angle X-ray scattering (SAXS) analysis unraveled the details of membrane (composed of either DMPC or POPC) fractionation pathways by SMA 3:1 [ 55 ] in which, two−four times more SMA(3:1) is required for lipids in the liquid crystalline phase than in the gel phase to get the lipid vesicles to form lipid-SMA nanodiscs.…”

Section: Synthetic Polymers For Reconstitution Of Membrane Assembliesmentioning

confidence: 99%

Current Developments in Native Nanometric Discoidal Membrane Bilayer Formed by Amphipathic Polymers

2021

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Unlike cytosolic proteins, membrane proteins (MPs) are embedded within the plasma membrane and the lipid bilayer of intracellular organelles. MPs serve in various cellular processes and account for over 65% of the current drug targets. The development of membrane mimetic systems such as bicelles, short synthetic polymers or amphipols, and membrane scaffold proteins (MSP)-based nanodiscs has facilitated the accommodation of synthetic lipids to stabilize MPs, yet the preparation of these membrane mimetics remains detergent-dependent. Bio-inspired synthetic polymers present an invaluable tool for excision and liberation of superstructures of MPs and their surrounding annular lipid bilayer in the nanometric discoidal assemblies. In this article, we discuss the significance of self-assembling process in design of biomimetic systems, review development of multiple series of amphipathic polymers and the significance of these polymeric “belts” in biomedical research in particular in unraveling the structures, dynamics and functions of several high-value membrane protein targets.

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“…In recent decades, researchers have shown interest in the synthesis of fluorescent polymers that have potential applications in pharmaceuticals and optical emission devices and utility as sensor probes due to their unique physicochemical properties [1,2]. In particular, the synthesis, characterization, and biological studies of cyanopyridine-based compounds remain topics of sustained interest [3,4].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Pyridine-Grafted Copolymers of Acrylic Acid–Styrene Derivatives for Antimicrobial and Fluorescence Applications

Durairaju

Chinnasamy²,

Rajabather

et al. 2021

Micromachines

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The goal of the present study was to copolymerize 3-(4-acetylphenylcarbamoyl) acrylic acid and styrene using azo-bis-isobutyronitrile (AIBN) as a catalyst. The resulting copolymers exhibited number average molecular weights (Mn) of 3.73–5.23 × 104 g/mol with a variable polydispersity (PDI = 2.3–3.8). The amide group of the PMA/PSA polymer was used for grafting poly (-styrene-maleic acid substituted aromatic 2-aminopyridine) by the Hantzsch reaction using a substituted aromatic aldehyde, malononitrile, and ammonium acetate. The polymer can emit strong blue fluorescence (λ = 510 nm) and its thermal stability and solubility were enhanced by polymer grafting. Moreover, the polymer showed the fluorescence spectra of the copolymer had a strong, broad emission band between 300 to 550 nm (maximum wavelength 538 nm) under excitation at 293 nm. The Hantzsch reaction yields an interesting class of nitrogen-based heterocycles that combine with a synthetic strategy for synthesis of grafted co-polymer pyridine-styrene derivatives. The as-prepared pyridine-based polymer compounds were screened against Gram-positive and Gram-negative bacteria, where a maximum inhibition zone toward all four types of bacteria was observed, including specific antifungal activity. Herein, a series of pyridine compounds were synthesized that showed enhanced fluorescent properties and antimicrobial properties due to their unique structure and ability to form polymer assemblies.

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Styrene maleic acid copolymer induces pores in biomembranes

Abstract: The experimental observations revealed that the interaction of styrene maleic acid with lipid membranes results in formation of toroidal pores.

Cited by 16 publications

References 33 publications

Conformational Tuning of Amylin by Charged Styrene-maleic-acid Copolymers

Conformational Tuning of Amylin by Charged Styrene-maleic-acid Copolymers

Current Developments in Native Nanometric Discoidal Membrane Bilayer Formed by Amphipathic Polymers

Synthesis and Characterization of Pyridine-Grafted Copolymers of Acrylic Acid–Styrene Derivatives for Antimicrobial and Fluorescence Applications

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