Inhibition of actin contractility reduces polyQ aggregate-induced rupture frequency. (A) Schematic representation of blebbistatin inhibition of myosin II resulting in reduced force transduction onto the nucleus. (B) Representative images of U2OS cells expressing polyQ74-NLS (green) and mCherry-cGAS (magenta) and treated with DMSO or blebbistatin. Orange arrowheads indicate nuclear mCherry-cGAS accumulation. (C) Quantification of the percentage of cells in B showing nuclear mCherry-cGAS accumulation after treatment with DMSO or blebbistatin (n_cells = 1,042, 978; N = 3). Dots represent averages of independent replicates grouped by shades of gray. Horizontal bars represent the mean. Scale bar represents 20 μm. ****P ≤ 0.0001, assessed by Fischer’s exact test.