Fig. 5: Mathematical modeling reliably predicts activator/sensitizer BH3-only synergies.
a Model extension for inclusion of BH3-only sensitizer. The sensitizer was implemented to reversibly bind Bcl-xL, with kinetics as measured in ref. 36. b Bax oligomerization predictions in response to Hrk peptide or tBid. Starting conditions were 50 nM Bax and 20 nM Bcl-xL. c Experimental validation of model predictions. Dose–response curves of calcein release from large unilamellar vesicles after incubation with 50 nM Bax, 20 nM Bcl-xL, and varying amounts of Hrk peptide or cBid (cleaved Bid, consisting of tBid and a p7 fragment). d Prediction of Bax oligomerization for single or combined addition of tBid and Hrk peptide, when added to a system of 20 nM Bcl-xL and 50 nM Bax. e Prediction of Bax oligomerization when not accounting for Bcl-xL mediated Bax retrotranslocation. f Experimental validation of model predictions. Bax pore formation was experimentally determined by release of calcein from large unilamellar vesicles (LUVs). LUVs were incubated with 20 nM Bcl-xL, 50 nM Bax, and cBid and/or Hrk peptide as indicated. Data are shown as means and SD of ensemble simulations or experimental data
