Liebig’s law of the minimum in the TGF-β/SMAD pathway
Fig 7
SMAD2 signaling responses are highly correlated with the amount of TGF-β receptors in single cells when TGFBR1 and TGFBR2 are expressed at a similar level.
(A) Model prediction for the correlation between SMAD2 N2C fold change response at 1 h and the number of TGF-β receptors when TGFBR1 and TGFBR2 are expressed at a similar level in single cells. The protein abundance values for TGFBR1 and TGFBR2 were set to be the same in single cell simulations (TGFBR1 to TGFBR2 expression ratio is 1). (B) Schematic representation of the optoTGFBRs optogenetic system. The development of the optoTGFBRs system was described in a previous publication [42]. (C) Illustration for the co-expression of optoTGFBR1 and optoTGFBR2-tdTomato with a 2A peptide element (P2A). (D) Time course profiles of iRFP-SMAD2 N2C fold change responses in individual optoTGFBRs-HeLa cells (n = 102) upon one pulse of blue light stimulation. (E) Representative live-cell images of SMAD2 responses to one pulse of blue light stimulation in single cells. The red, green and blue arrows indicate cells that express optoTGFBR2-tdTomato receptor at a high, intermediate and low level, respectively. (F) The plot of iRFP-SMAD2 N2C fold change responses at 20 min versus the expression of optoTGFBR2-tdTomato before blue light stimulation (0 h) in optoTGFBRs-HeLa cells.(G) The plot of iRFP-SMAD2 N2C fold change responses at 1 h versus the expression of optoTGFBR2-tdTomato before blue light stimulation (0 h) in optoTGFBRs-HeLa cells. The correlations (R-values and p-values) in the plots were calculated with Pearson correlation coefficients.