Graphene oxide as antibacterial sensitizer: Mechanically disturbed cell membrane for enhanced poration efficiency of melittin

Xiao, Shufeng; Lu, Xuemei; Gou, Lu; Li, Jingliang; Ma, Yu‐qiang; Liu, Jiaojiao; Yang, Kai; Yuan, Bing

doi:10.1016/j.carbon.2019.04.067

Cited by 31 publications

(30 citation statements)

References 44 publications

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“…To engineer melittin with nanomaterials is also an intriguing pathway to improve the performance of melittin. It has been shown that the bacteria-killing efficacy of AMPs could be improved by decorating the peptides on the nanoparticle surface or self-assembling the AMP-based derivatives into nanostructures [41,106,107,108,109,110,111,112,113,114,115]. The improved bacteria-killing ability is mostly induced by the increased local peptide concentration of AMPs, which strengthens the potential cooperation between peptides.…”

Section: Discussionmentioning

confidence: 99%

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How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane

Hong

Deng

et al. 2019

Molecules

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Antimicrobial peptides (AMPs), as a key component of the immune defense systems of organisms, are a promising solution to the serious threat of drug-resistant bacteria to public health. As one of the most representative and extensively studied AMPs, melittin has exceptional broad-spectrum activities against microorganisms, including both Gram-positive and Gram-negative bacteria. Unfortunately, the action mechanism of melittin with bacterial membranes, especially the underlying physics of peptide-induced membrane poration behaviors, is still poorly understood, which hampers efforts to develop melittin-based drugs or agents for clinical applications. In this mini-review, we focus on recent advances with respect to the membrane insertion behavior of melittin mostly from a computational aspect. Membrane insertion is a prerequisite and key step for forming transmembrane pores and bacterial killing by melittin, whose occurrence is based on overcoming a high free-energy barrier during the transition of melittin molecules from a membrane surface-binding state to a transmembrane-inserting state. Here, intriguing simulation results on such transition are highlighted from both kinetic and thermodynamic aspects. The conformational changes and inter-peptide cooperation of melittin molecules, as well as melittin-induced disturbances to membrane structure, such as deformation and lipid extraction, are regarded as key factors influencing the insertion of peptides into membranes. The associated intermediate states in peptide conformations, lipid arrangements, membrane structure, and mechanical properties during this process are specifically discussed. Finally, potential strategies for enhancing the poration ability and improving the antimicrobial performance of AMPs are included as well.

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Section: Discussionmentioning

confidence: 99%

“…Among these factors, peptide concentration is the most important. It has been proven that the transition occurs only when the peptide-to-lipid ratio, normalP/normalL, is higher than a threshold value [32,37,41]. Furthermore, the normalP/normalL threshold is dependent on lipid composition [38].…”

Section: Introductionmentioning

confidence: 99%

How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane

Hong

Deng

et al. 2019

Molecules

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“…The first one concerns the mechanical damage to the bacterial cell walls, which in turn leads to metabolic disorders, oxidative stress, and cell death. This process is widely described by many researchers, among others in [ 47 , 48 ]. The second mechanism of GO influence on microorganisms is relatively little known.…”

Section: Resultsmentioning

confidence: 99%

Nanocomposite Cellulose Fibres Doped with Graphene Oxide and Their Biocidal Properties

et al. 2021

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The paper presents a method of obtaining composite cellulose fibres (CEL) doped with graphene oxide (GO) and the influence of GO nanoparticles on the structure and properties of the obtained fibres. Composite fibres (GO/CEL) were prepared using wet method from 5% CEL solutions in 1-ethyl-3-methylimidazolium acetate (EMIMAc) containing GO (0; 0.21; 0.50; 0.98; 1.97% w/w) dispersion in N,N-dimethylformamide (DMF). The fibres were coagulated in distilled water and methanol. Optical microscopy allowed us to demonstrate a good degree of GO additive dispersion in the CEL matrix. Surface morphology was examined by scanning electron microscopy (SEM) and infrared spectroscopy (FTIR), which indicated interactions between the matrix and the additive. Strength tests have shown that GO/CEL fibres are characterised by high values of elongation at break (7.7–19.5%) and tenacity (~133–287 [MPa]). The obtained composite fibres are characterized by good biocidal properties against Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphilococcus aureus), and fungi Candida albicans, and the resistance to microorganisms depends on the surface zeta potential value and the isoelectric point (IEP) of GO/CEL fibres.

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“…GUVs, composed of pure DOPC or DOPC/Chol (at 7:3 by ratio), were prepared following the conventional electroformation method ( Lu et al, 2019b ; Xiao et al, 2019 ), washed with centrifugation (8000 rpm × 20 min, for three times), and diluted to a final concentration of ≈ 0.02 mg lipid per mL for use. The GUVs were then moved to a home-made cell, immobilized on the substrate surface for an in situ observation under confocal microscopy (LSM 710, Zeiss).…”

Section: Methodsmentioning

confidence: 99%

“…Antibiotic resistance crisis has becoming a world-wide healthcare threat for human beings and therefore the development of new bactericides is urgently needed ( Willyard, 2017 ; Lam et al, 2016 ). Antimicrobial peptides (AMPs), an effective weapon of the innate immune system to protect the host from bacterial invasion, promise a fundamental resolution to this serious issue ( Lu et al, 2019b ; Munguia and Nizet, 2017 ; Sancho-Vaello and Zeth, 2015 ; Xiao et al, 2019 ; Zhang et al, 2018 ). AMPs kill bacteria by directly permeabilizing the bacterial membranes leading to leakage of cellular content ( Hong et al, 2019 ; Lee et al, 2013 ; Ma et al, 2020 ; Wimley, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Cholesterols Work as a Molecular Regulator of the Antimicrobial Peptide-Membrane Interactions

Chen

et al. 2021

Front. Mol. Biosci.

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The existing cholesterols (Chols) in animal cell membranes play key roles in many fundamental cellular processes, which also promise the possibility to modulate the bioactivity of various membrane-active biomacromolecules. Here, combining dynamic giant unilamellar vesicle leakage experiments and molecular dynamics simulations, the inhibitory effect of Chols on the membrane poration activity of melittin (Mel), a typical natural antimicrobial peptide, is demonstrated. Molecular details of the Mel-Chol interactions in membrane show that, for a Chol-contained lipid membrane, Mel exposure would perturb the symmetric bilayer structure of the membrane and specifically influence the location and orientation distributions of Chol molecules to an asymmetric state between the two leaflets; moreover, the Mel-Chol interactions are significantly influenced by the membrane environment such as unsaturation degree of the lipid components. Such inhibitory effect is normally ascribed to an accumulation of Chol molecules around the membrane-bound peptide chains and formation of Chol-Mel complexes in the membrane, which hinder the further insertion of peptides into the membrane. This work clarifies the molecular interactions between membrane-active peptides and Chol-contained membranes, and suggest the possibility to develop targeted drugs due to the membrane component specificity between bacterial and animal cells.

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Graphene oxide as antibacterial sensitizer: Mechanically disturbed cell membrane for enhanced poration efficiency of melittin

Cited by 31 publications

References 44 publications

How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane

How Melittin Inserts into Cell Membrane: Conformational Changes, Inter-Peptide Cooperation, and Disturbance on the Membrane

Nanocomposite Cellulose Fibres Doped with Graphene Oxide and Their Biocidal Properties

Cholesterols Work as a Molecular Regulator of the Antimicrobial Peptide-Membrane Interactions

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