Fig. 1: Modulating the cytotoxicity of IAPP fibrils with an N-to-Q substitution at position 21.

a SS-NMR and cryo-EM molecular models of IAPP secondary structure in amyloid fibrils showing the side chain of Asn2129, 31. b Representative TEM images of IAPP and N21Q fibrils. Scale bar: 100 nm. c INS-1E cells were incubated for 24 h with pre-assembled fibrils. d Caspase-3 activation over treatment time of INS-1E cells incubated with 50 µM fibrils. c, d Data represent mean ± S.D. of at least three independent experiments performed in triplicate. e Representative fluorescence microscopy images showing the distribution of live (green) and dead (red) INS-1E cells after treatment with 50 µM fibrils for 24 h. Scale bar: 50 µm. b–e Fibrils were assembled from freshly dissolved monomerized peptides incubated under quiescent conditions for 48 h at a concentration of 150 µM in 20 mM Tris-HCl buffer, pH 7.4.