Dataset Information

Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated ?-Amyloid Oligomers.

ABSTRACT: Nonfibrillar ?-amyloid (A?) oligomers are considered as major neurotoxic species in the pathology of Alzheimer's disease. The presence of A? oligomers was shown to cause membrane disruptions in a broad range of model systems. However, the molecular basis of such a disruption process remains unknown. We previously demonstrated that membrane-incorporated 40-residue A? (A?40) oligomers could form coaggregates with phospholipids. This process occurred more rapidly than the fibrillization of A?40 and led to more severe membrane disruption. The present study probes the time-dependent changes in lipid dynamics, bilayer structures, and peptide-lipid interactions along the time course of the oligomer-induced membrane disruption, using solid-state NMR spectroscopy. Our results suggest the presence of certain intermediate states with phospholipid molecules entering the C-terminal hydrogen-bonding networks of the A?40 oligomeric cores. This work provides insights on the molecular mechanisms of A?40-oligomer-induced membrane disruption.

SUBMITTER: Qiang W

PROVIDER: S-EPMC7647725 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated β-Amyloid Oligomers.

Qiang Wei W Doherty Katelynne E KE Klees Lukas M LM Tobin-Miyaji Yuto Y

The journal of physical chemistry letters 20200918 19

Nonfibrillar β-amyloid (Aβ) oligomers are considered as major neurotoxic species in the pathology of Alzheimer's disease. The presence of Aβ oligomers was shown to cause membrane disruptions in a broad range of model systems. However, the molecular basis of such a disruption process remains unknown. We previously demonstrated that membrane-incorporated 40-residue Aβ (Aβ<sub>40</sub>) oligomers could form coaggregates with phospholipids. This process occurred more rapidly than the fibrillization ...[more]

PMID: 32931283

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Project description:The luminescent, mono-diimine ruthenium complexes [(H)Ru(CO)(PPh3)2(dcbpy)][PF6] (1) (dcbpy = 4,4'-dicarboxy-2,2'-bipyridyl) and [(H)Ru(CO)(dppene)(5-amino-1,10-phen)][PF6] (2) (dppene = bis(diphenylphosphino)ethylene; phen = phenanthroline) were conjugated with 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DPPE) and with cholesterol in the case of complex 2. Using standard conjugation techniques, compound 1 gives the bis-lipid derivative [(H)Ru(CO)(PPh3)2(dcbpy-N-DPPE2)][PF6] (3), while 2 provides the monolipid conjugate [(H)Ru(CO)(dppene)(1,10-phen-5-NHC(S)-N-DPPE)][PF6] (4) and the cholesterol derivative [(H)Ru(CO)(dppene)(1,10-phen-5-NHC(O)Ocholesteryl)][PF6] (5). These compounds were characterized by spectroscopic methods, and their photophysical properties were measured in organic solvents. The luminescence of lipid conjugates 3 and 4 is quenched in organic solvents while compound 4 shows a weak, short-lived, blue-shifted emission in aqueous solution. The cholesterol conjugate 5 shows the long-lived, microsecond-time scale emission associated with triplet metal-to-ligand charge-transfer excited states. Incorporation of conjugate 3 in lipid bilayer vesicles restores the luminescence, but with blue shifts (~80 nm) accompanied by nanosecond-time scale lifetimes. In the vesicles conjugate 4 shows a short-lived and blue-shifted emission similar to that observed in solution but with increased intensity. Conjugation of the complex [(H)Ru(CO)(PhP2C2H4C(O)O-N-succinimidyl)2(bpy)][PF6] (6") (bpy = 2,2'-bipyridyl) with DPPE gives the phosphine-conjugated complex [(H)Ru(CO)(PhP2C2H4C(O)-N-DPPE)2(bpy)][PF6] (7). Complex 7 also exhibits a short-lived and blue-shifted emission in solution and in vesicles as observed for complexes 3 and 4. We have also conjugated the complex [Ru(bpy)2(5-amino-1,10-phen)][PF6]2 (8) with both cholesterol (9) and DPPE (10). Neither complex 9 nor the previously reported complex 10 exhibited the blue shifts observed for complexes 3 and 4 when incorporated into large unilamellar vesicles (LUVs). The anisotropies of the emissions of complexes 3, 4, and 7 were also measured in LUVs, and those of complex 5 were measured in both glycerol and LUVs. High fundamental anisotropies were observed for complexes 3, 4, and 7.

Dataset Information

Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated ?-Amyloid Oligomers.

Publications

Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated β-Amyloid Oligomers.

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