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The binding of monomeric and aggregated variants of 1-83 N-terminal fragment of apolipoprotein A-I with substitution mutations G26R, G26R/W@8, G26R/W@50 and G26R/W@72 to the model lipid membranes composed of phosphatidylcholine and its mixture with cholesterol has been investigated using fluorescent probes pyrene and Laurdan. Examination of pyrene spectral behavior did not reveal any marked influence of apoA-I mutants on the hydrocarbon region of lipid bilayer. In contrast, probing the membrane effects by Laurdan revealed decrease in the probe generalized polarization in the presence of aggregated proteins. suggesting that oligomeric and fibrillar apoA-I species induce increase in hydration degree and reduction of lipid packing density in the membrane interfacial region. These findings may shed light on molecular details of amyloid cytotoxicity. [ABSTRACT FROM AUTHOR]

Highlights: [•] The N-terminal 1–83 residues of apoA-I have a propensity to form amyloid fibrils. [•] ApoA-I 1–43 peptide forms amyloid fibrils with transition to β-sheet-rich structure. [•] The G26R point mutation enhances the fibril formation of apoA-I 1–43 peptide. [•] The extreme N-terminal region plays a crucial role in fibril formation by apoA-I. [ABSTRACT FROM AUTHOR]