Effects of Cholesterol on Amyloid-induced Membrane Poration
Yang, Y.; Shah, B.; Agapito, M.; Nieuwkoop, A.
Show abstract
The aggregation of amyloid peptides and their interactions with lipid membranes are central to the pathology of several neurodegenerative diseases. Using all-atom molecular dynamics simulations, we investigate how varying cholesterol concentrations (0%, 15%, and 30%) modulate amyloid-induced membrane poration. In cholesterol-free bilayers, pore formation was reproducibly observed in all simulations, whereas the presence of 15% cholesterol significantly reduced pore incidence, and 30% cholesterol entirely suppressed pore formation. Analysis revealed that cholesterol stiffens the bi-layer and strongly inhibits peptide-induced perturbations. Furthermore, cholesterol reduced the inter-leaflet mechanical coupling critical for transmembrane {beta}-sheet formation, a key step in pore initiation. Our findings suggest that increasing cholesterol content protects membranes against amyloid-induced poration, providing a potential molecular basis for the observed reduction in amyloid toxicity in cholesterol-enriched environments. These results offer new insights into the complex role of membrane com-position in amyloid-related diseases and highlight cholesterol as a potential modulator of amyloid cytotoxicity.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Intrinsically disordered membrane anchors of Rheb, RhoA and DiRas3 small GTPases: Molecular dynamics, membrane organization, and interactions 97%
- Physical Characterization of Triolein and Implications for Its Role in Lipid Droplet Biogenesis 97%
- Breakage of Hydrophobic Contacts Limits the Rate of Passive Lipid Exchange Between Membranes 96%
Similar papers in this journal
- How cell penetrating peptides behave differently from pore forming peptides: structure and stability of induced transmembrane pores 96%
- Hydration layer of only few molecules controls lipid mobility in biomimetic membranes 95%
- Strikingly different roles of SARS-CoV-2 fusion peptides uncovered by neutron scattering 94%
Similar papers in this journal
- Alanine Scanning to Define Membrane Protein-Lipid Interaction Sites Using Native Mass Spectrometry 95%
- Temporin B forms hetero-oligomers with Temporin L, modifies its membrane activity and increases the cooperativity of its antibacterial pharmacodynamic profile 94%
- Atomistic Insights into gp82 Binding: A Microsecond, Million-Atom Exploration of Trypanosoma cruzi Host-Cell Invasion 93%
Similar papers in this journal
- The molecular mechanism of lipid uptake by membrane-anchored bridge-like lipid transfer proteins. 96%
- Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane 95%
- The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.