The pathology of Alzheimer’s disease is linked to interactions between various types of assemblies of amyloid-beta (Aβ) peptides (e.g., oligomers, channels and fibrils) and neural cell membranes, which directly affect membrane integrity. We use molecular dynamics simulations to unravel the details of the specific molecular interactions between Aβ peptides and lipid membranes. In the first part of this study we test the stability of transmembrane Aβ1-42 oligomers and investigate how the interplay between Aβ and membranes is affected by the secondary structure, degree of oligomerization and mutations of Aβ as well as the membrane composition.[1,2] The main findings are that β-sheet tetramers are stable within the membrane and that they are sufficient to cause membrane damage while transmembrane Aβ monomers do not perturb the membrane sufficiently to make them permeable.[1] The membrane damaging effect of the β-sheet tetramers is further enhanced by Aβ mutations (e.g., the “arctic” E22G mutation), and may explain the higher toxicity of these mutants compared to wild-type Aβ peptides.[2] In the second part of this study we analyze how the membrane surface affects the aggregation of Aβ. [1] C. Poojari, A. Kukol and B. Strodel, BBA-Biomembranes 1828: 327-339 (2013) [2] C. Poojari and B. Strodel, PLoS ONE 8: e78399 (2013)

Revealing the interplay between amyloid-β and membranes through molecular simulations

249th National Meeting (2015)

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Revealing the interplay between amyloid-β and membranes through molecular simulations<br />