Fig. 5: GA DPRs oligomers permeabilize the nuclear membrane.

a Representative images of lamin B1 staining on digitonin-treated SH-SY5Y cells in the presence of GA DPRs oligomers (upper row), fibrils (middle), or mock (buffer only, bottom row). The nuclei were counterstained with DAPI. Scale bars indicate 10 μm. b Quantification analysis of SH-SY5Y cell nuclei with lamin B1 staining. Three biological replicates were carried out (r = 3). More than 27 cells were counted and analyzed in each group (n ≥ 27). Mean and standard deviation for mock = 13.9 ± 7.8; Triton = 96.9 ± 2.4; GA DPRs oligomers = 62.3 ± 23.9; GA DPRs fibrils = 9.5 ± 6.2; ADP-3 + UV = 10.6 ± 4.2. * indicates statistical significance where p value < 0.05 and ** indicates statistical significance where p value < 0.01 (analyzed by two-sided Welch’s T test with Bonferroni correction, test statistic in group comparison between mock and GA DPRs oligomers: p value = 0.009, degree of freedom = 4, t value = 2.77; group comparison between GA DPRs Oligomers and GA DPRs fibrils: p value = 0.011, degree of freedom = 3, t value = 3.18). c The ratio of the calcein (emission at 520 nm) leak-out from lipid-based liposome based on the fluorescence measurement. Fluorescence intensity was measured for each sample, and then subtracts from the background (liposome only) and normalized to the signal from the Triton X100 treatment (lysed liposome). Three experiment replicates were carried out (r = 3), Mean and standard deviation for GA DPRs oligomers = 32.4 ± 2.6; GA DPRs fibrils = 5.2 ± 0.8. ** indicates statistical significance where p value < 0.01 (analyzed by two-sided Welch’s T test, p value = 0.003, degree of freedom = 2, t value = 4.30).