Fig. 1: Pharmacological stimuli result in net increases in the TPE-MI reactivity of cellular proteins.

a Structure of tetraphenylethene conjugated to a maleimide (TPE-MI). TPE-MI is inherently non-fluorescent in the free form, forming a fluorescent conjugate upon binding exposed thiol residues within polypeptides. b Method schematic for quantifying global proteome conformation. Neuro-2a cells were treated with MG132, VER155008, staurosporine, celastrol, novobiocin, or the vehicle control (milliQ water in the case of Novobiocin, else DMSO), before labeling with TPE-MI. Cells were then analyzed via flow cytometry. c Median TPE-MI fluorescence measured at 450 nm, normalized to the vehicle-treated control population. Shown are boxplots overlayed with individual datapoints of at least four biological replicates (dots; novobiocin n = 6, staurosporine n = 5, otherwise n = 4), *p < 0.05, **p < 0.01, ***p < 0.001 according to one-sample t-test against a hypothetical mean of 1. In c, individual points are overlayed on boxplots displayed as follows: center line corresponds to the median; box limits display upper and lower quartiles; and where shown, whiskers extend to the last or first data point that is within 1.5× the interquartile range of the box limits in the upper and lower directions, respectively. Source data are provided as a Source Data file.