Structural changes introduced by cholesterol and melatonin to the model membranes mimicking preclinical conformational diseases

Murugova, T. N.; Ivankov, Oleksandr I.; Ermakova, E. V.; Kondela, Tomáš; Hrubovčák, Pavol; Skoi, V. V.; Kučerka, Norbert

doi:10.4149/gpb_2019054

Cited by 15 publications

(9 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The membrane thicknesses were obtained at rst from the small-angle Kratky-Porod approximation for unoriented lamellar objects 20 . This approach is very sensitive to a possible Bragg-scattering peak that would skew the data analysis.…”

Section: Resultsmentioning

confidence: 99%

Amyloid-beta peptide (25-35) triggers a reorganization of lipid membranes driven by temperature changes

Ivankov

Murugova

Ermakova

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

The amyloid-beta peptide (Aβ) is considered a key factor in Alzheimer's disease (AD) ever since the discovery of the disease. The understanding of its damaging influence has however shifted recently from large fibrils observed in the inter-cellular environment to the small oligomers interacting with a cell membrane. We studied the effect of temperature on the latter interactions by evaluating the structural characteristics of zwitterionic phosphatidylcholine (PC) membranes with incorporated Aβ25-35 peptide. By means of small angle neutron scattering (SANS), we have observed for the first time a spontaneous reformation of extruded unilamellar vesicles (EULVs) to discoidal bicelle-like structures (BLSs) and small unilamellar vesicles (SULVs). These changes in the membrane self-organization happen during the thermodynamic phase transitions of lipids and only in the presence of the peptide. We interpret the dramatic changes in the membrane's overall shape with parallel changes in its thickness as the Aβ25-35 triggered membrane damage and a consequent reorganization of its structure. The suggested process is consistent with an action of separate peptides or a small number of peptide oligomers rather than the result of a large Aβ fibril.

show abstract

Section: Resultsmentioning

confidence: 99%

Amyloid-beta peptide (25-35) triggers a reorganization of lipid membranes driven by temperature changes

Ivankov

Murugova

Ermakova

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The membrane properties, and fluidity in particular, are being scrutinized for possibly governing the amyloid aggregation. 9 It is well-known that ions penetrate into the membrane and bind to the carbonyl and phosphate regions of the polar phospholipid head groups affecting the membrane fluidity, bending, hydration, and strength. 10−15 Many mono-and divalent metal ions such as sodium, potassium, magnesium, and calcium are present in intra-and extracellular space at high concentrations while, for example, cobalt, zinc, and iron are found at lower concentrations.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The data indicate the destabilization of neuronal calcium homeostasis and suggest that the molecular basis in this mechanism is lying within the lipid–peptide–ion interactions. The membrane properties, and fluidity in particular, are being scrutinized for possibly governing the amyloid aggregation …”

Section: Introductionmentioning

confidence: 99%

Cation–Zwitterionic Lipid Interactions Are Affected by the Lateral Area per Lipid

Kučerka

Ermakova²,

Dushanov

et al. 2020

Langmuir

Self Cite

View full text Add to dashboard Cite

Interactions of the divalent cations Ca2+ and Mg2+ with the zwitterionic lipid bilayers prepared of a fully saturated dipalmitoylphosphatidylcholine (DPPC) or a di-monounsaturated dioleoylphosphatidylcholine (DOPC) were studied by using the neutron scattering methods and molecular dynamics simulations. The effect on the bilayer structural properties confirms the direct interactions in all cases studied. The changes are observed in the bilayer thickness and lateral area. The extent of these structural changes, moreover, suggests various mechanisms of the cation–lipid interactions. First, we have observed a small difference when studying DPPC bilayers in the gel and fluid phases, with somewhat larger effects in the former case. Second, the hydration proved to be a factor in the case of DOPC bilayers, with the larger effects in the case of less hydrated systems. Most importantly, however, there was a qualitative difference between the results of the fully hydrated DOPC bilayers and the others examined. These observations then prompt us to suggest an interaction model that is plausibly governed by the lateral area of lipid, though affected indirectly also by the hydration level. Namely, when the interlipid distance is small enough to allow for the multiple lipid–ion interactions, the lipid–ion–lipid bridges are formed. The bridges impose strong attractions that increase the order of lipid hydrocarbon chains, resulting in the bilayer thickening. In the other case, when the interlipid distance extends beyond a limiting length corresponding to the area per lipid of ∼65 Å2, Mg2+ and Ca2+ continue to interact with the lipid groups by forming the separate ion–lipid pairs. As the interactions proposed affect the lipid membrane structure in the lateral direction, they may prove to play their role in other mechanisms lying within the membrane multicomponent systems and regulating for example the lipid–peptide–ion interactions.

show abstract

“…The membrane thicknesses were obtained at first from the small-angle Kratky–Porod approximation for unoriented lamellar objects 24 . This approach is very sensitive to a possible Bragg-scattering peak that would skew the data analysis.…”

Section: Resultsmentioning

confidence: 99%

Amyloid-beta peptide (25–35) triggers a reorganization of lipid membranes driven by temperature changes

Ivankov

Murugova

Ermakova

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

The amyloid-beta peptide (Aβ) is considered a key factor in Alzheimer's disease (AD) ever since the discovery of the disease. The understanding of its damaging influence has however shifted recently from large fibrils observed in the inter-cellular environment to the small oligomers interacting with a cell membrane. We studied the effect of temperature on the latter interactions by evaluating the structural characteristics of zwitterionic phosphatidylcholine (PC) membranes with incorporated Aβ25–35 peptide. By means of small angle neutron scattering (SANS), we have observed for the first time a spontaneous reformation of extruded unilamellar vesicles (EULVs) to discoidal bicelle-like structures (BLSs) and small unilamellar vesicles (SULVs). These changes in the membrane self-organization happen during the thermodynamic phase transitions of lipids and only in the presence of the peptide. We interpret the dramatic changes in the membrane's overall shape with parallel changes in its thickness as the Aβ25–35 triggered membrane damage and a consequent reorganization of its structure. The suggested process is consistent with an action of separate peptides or small size peptide oligomers rather than the result of large Aβ fibrils.

show abstract

Structural changes introduced by cholesterol and melatonin to the model membranes mimicking preclinical conformational diseases

Cited by 15 publications

References 54 publications

Amyloid-beta peptide (25-35) triggers a reorganization of lipid membranes driven by temperature changes

Amyloid-beta peptide (25-35) triggers a reorganization of lipid membranes driven by temperature changes

Cation–Zwitterionic Lipid Interactions Are Affected by the Lateral Area per Lipid

Amyloid-beta peptide (25–35) triggers a reorganization of lipid membranes driven by temperature changes

Contact Info

Product

Resources

About