Modulation of lipid membrane structural and mechanical properties by a peptidomimetic derived from reduced amide scaffold

Khadka, Nawal K.; Teng, P. K.; Cai, Jianfeng; Pan, Jianjun

doi:10.1016/j.bbamem.2017.01.026

Cited by 19 publications

(26 citation statements)

References 97 publications

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“…The insensitivity of s 0 highlights that PrP106-126 does not markedly alter the thickness of the POPC bilayer. Using force spectroscopy measurements, we have observed a similar resilience of the bilayer thickness to the treatment of an antimicrobial peptidomimetic 46 . Interestingly, introducing ethanol to mica-supported planar bilayers caused a stark decrease of the bilayer thickness as indicated by the shifting of force curves toward smaller s 59 .…”

Section: Resultsmentioning

confidence: 72%

“…S4, Supporting Information). Using fusogenic calcium ions, we have shown that lipid molecules extracted from planar bilayers can form a second layer on top of the original bilayer 46 . The process of forming a second layer is reminiscent of the formation of a mica-supported bilayer.…”

Section: Discussionmentioning

confidence: 99%

“…A Multimode 8 AFM (Bruker, Santa Barbara, CA) and a Nanoscope V controller are used for solution AFM imaging (room temperature). Experimental procedure has been reported elsewhere 40–46 . Planar bilayers are formed by the vesicle rupture and fusion mechanism on a freshly cleaved mica film 47–48 .…”

Section: Methodsmentioning

confidence: 99%

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Membrane Disruption Mechanism of a Prion Peptide (106–126) Investigated by Atomic Force Microscopy, Raman and Electron Paramagnetic Resonance Spectroscopy

Pan¹,

Sahoo²,

Dalzini

et al. 2017

J. Phys. Chem. B

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A fragment of the human prion protein spanning residues 106-126 (PrP106-126) recapitulates many essential properties of the disease-causing protein such as amyloidogenicity and cytotoxicity. PrP106-126 has an amphipathic characteristic that resembles many antimicrobial peptides (AMPs). Therefore, the toxic effect of PrP106-126 could arise from a direct association of monomeric peptides with membrane matrix. Several experimental approaches are employed to scrutinize the impacts of monomeric PrP106-126 on model lipid membranes. Porous defects in planar bilayers are observed by using solution atomic force microscopy. Adding cholesterol does not impede defect formation. Force spectroscopy experiment shows that PrP106-126 reduces Young’s modulus of planar lipid bilayers. We use Raman microspectroscopy to study the effect of PrP106-126 on lipid vibrational dynamics. For phosphatidylcholine lipids, PrP106-126 disorders the intra-chain conformation, while the inter-chain interaction is not altered; for phosphatidylethanolamine lipids, PrP106-126 increases the inter-chain interaction, while the intra-chain conformational order remains similar. We explain the observed differences by considering different modes of peptide insertion. Finally, electron paramagnetic resonance spectroscopy shows that PrP106-126 progressively decreases the orientational order of lipid acyl chains in magnetically aligned bicelles. Together, our experimental data support the proposition that monomeric PrP106-126 can disrupt lipid membranes by using similar mechanisms found in AMPs.

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Section: Resultsmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

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Membrane Disruption Mechanism of a Prion Peptide (106–126) Investigated by Atomic Force Microscopy, Raman and Electron Paramagnetic Resonance Spectroscopy

Pan¹,

Sahoo²,

Dalzini

et al. 2017

J. Phys. Chem. B

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“…A maximum force called the puncture force is reached when the bilayer is punctured by the tip (indicated by arrowheads in Fig. 3) [29]. For the intact bilayer, the puncture force is ~3 nN and the bilayer puncture takes place at a distance of ~4 nm away from the mica surface (located at zero distance).…”

Section: Resultsmentioning

confidence: 99%

Cholesterol and phosphatidylethanolamine lipids exert opposite effects on membrane modulations caused by the M2 amphipathic helix

Pan¹,

Dalzini²,

Song³

2019

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Membrane curvature remodeling induced by amphipathic helices (AHs) is essential in many biological processes. Here we studied a model amphipathic peptide, M2AH, derived from influenza A M2. We are interested in how M2AH may promote membrane curvature by altering membrane physical properties. We used atomic force microscopy (AFM) to examine changes in membrane topographic and mechanical properties. We used electron paramagnetic resonance (EPR) spectroscopy to explore changes in lipid chain mobility and chain orientational order. We found that M2AH perturbed lipid bilayers by generating nanoscale pits. The structural data are consistent with lateral expansion of lipid chain packing, resulting in a mechanically weaker bilayer. Our EPR spectroscopy showed that M2AH reduced lipid chain mobility and had a minimal effect on lipid chain orientational order. The EPR data are consistent with the surface-bound state of M2AH that acts as a chain mobility inhibitor. By comparing results from different lipid bilayers, we found that cholesterol enhanced the activity of M2AH in inducing bilayer pits and altering lipid chain mobility. The results were explained by considering specific M2AH-cholesterol recognition and/or cholesterol-induced expansion of interlipid distance. Both AFM and EPR experiments revealed a modest effect of anionic lipids. This highlights that membrane interaction of M2AH is mainly driven by hydrophobic forces. Lastly, we found that phosphatidylethanolamine (PE) lipids inhibited the activity of M2AH. We explained our data by considering interlipid hydrogen-bonding that can stabilize bilayer organization. Our results of lipid-dependent membrane modulations are likely relevant to M2AH-induced membrane restructuring.

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“…We have previously used this method to evaluate changes in bilayer permeability caused by different compounds. 38−40…”

Section: Resultsmentioning

confidence: 99%

Lipopolysaccharide-Dependent Membrane Permeation and Lipid Clustering Caused by Cyclic Lipopeptide Colistin

2018

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Polyanionic lipopolysaccharides (LPS) play an important role in regulating the permeability of the outer membrane (OM) of Gram-negative bacteria. Impairment of the LPS-enriched OM is essential in initiating the bactericidal activity of polymyxins. We are interested in how colistin (polymyxin E) affects the membrane permeability of LPS/phospholipid bilayers. Our vesicle leakage experiment showed that colistin binding enhanced bilayer permeability; the maximum increase in the bilayer permeability was positively correlated with the LPS fraction. Addition of magnesium ions abolished the effect of LPS in enhancing bilayer permeabilization. To describe the vesicle leakage behavior from a structural perspective, we performed liquid atomic force microscopy (AFM) measurements on planar lipid bilayers. We found that colistin caused the formation of nano- and macroclusters that protruded from the bilayer by ∼2 nm. Moreover, cluster development was promoted by increasing the fraction of LPS or colistin concentration but inhibited by magnesium ions. To explain our experimental data, we proposed a lipid clustering model where colistin binds to LPS to form large-scale complexes segregated from zwitterionic phospholipids. The discontinuity (and thickness mismatch) at the edge of LPS–colistin clusters will create a passage that allows solutes to permeate through. The proposed model is consistent with all data obtained from our leakage and AFM experiments. Our results of LPS-dependent membrane restructuring provided useful insights into the mechanism that could be used by polymyxins in impairing the permeability barrier of the OM of Gram-negative bacteria.

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Modulation of lipid membrane structural and mechanical properties by a peptidomimetic derived from reduced amide scaffold

Cited by 19 publications

References 97 publications

Membrane Disruption Mechanism of a Prion Peptide (106–126) Investigated by Atomic Force Microscopy, Raman and Electron Paramagnetic Resonance Spectroscopy

Membrane Disruption Mechanism of a Prion Peptide (106–126) Investigated by Atomic Force Microscopy, Raman and Electron Paramagnetic Resonance Spectroscopy

Cholesterol and phosphatidylethanolamine lipids exert opposite effects on membrane modulations caused by the M2 amphipathic helix

Lipopolysaccharide-Dependent Membrane Permeation and Lipid Clustering Caused by Cyclic Lipopeptide Colistin

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