Retardation of Abeta fibril formation by phospholipid vesicles depends on membrane phase behavior.
An increasing amount of evidence suggests that in several amyloid diseases, the fibril formation in vivo and the mechanism of toxicity both involve membrane interactions. We have studied Alzheimer's disease related amyloid beta peptide (Abeta). Recombinant Abeta(M1-40) and Abeta(M1-42) produced in Escherichia coli, allows us to carry out large scale kinetics assays with good statistics. The amyloid formation process is followed in means of thioflavin T fluorescence at relatively low (down to 380 nM) peptide concentration approaching the physiological range. The lipid membranes are introduced in the system as large and small unilamellar vesicles. The aggregation lagtime increases in the presence of lipid vesicles for all situations investigated and the phase behavior of the membrane in the vesicles has a large effect on the aggregation kinetics. By comparing vesicles with different membrane phase behavior we see that the solid gel phase dipalmitoylphosphatidylcholine bilayers cause the largest retardation of Abeta fibril formation. The membrane-induced retardation reaches saturation and is present when the vesicles are added during the lag time up to the nucleation point. No significant difference is detected in lag time when increasing amount of negative charge is incorporated into the membrane.
Hellstrand
Erik
E
Department of Biophysical Chemistry, Lund University, Lund, Sweden. erik.hellstrand@bpc.lu.se
Sparr
Emma
E
Linse
Sara
S
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D000682:Amyloid / Q000009:adverse effects*; D016229:Amyloid beta-Peptides / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry; D010743:Phospholipids / Q000494:pharmacology*; D011487:Protein Conformation; D022142:Secretory Vesicles
D000682:Amyloid; D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D008055:Lipids; D008563:Membrane Lipids; D010743:Phospholipids