Fig. 1: Stiffening extracellular matrix lowers pHi in metastatic human lung carcinoma (H1299). | Cell Death & Disease

Fig. 1: Stiffening extracellular matrix lowers pHi in metastatic human lung carcinoma (H1299).

From: Intracellular pH dynamics respond to extracellular matrix stiffening and mediate vasculogenic mimicry through β-catenin

Fig. 1

a Schematic of increased pHi and ECM stiffening (via increased protein secretion and increased protein crosslinking) associated with tumorigenesis. b Schematic of synthetic ECM models with tunable-stiffness ( ~ 50 Pa–1500 Pa). The hyaluronic acid (HA) gel system mimics increased ECM protein crosslinking while the Matrigel (or Geltrex) model mimics increased ECM protein secretion. c Representative images of H1299 cells stably expressing mCherry-pHluorin pH biosensor plated on varying HA gel stiffnesses. Images show ratiometric display of pHluorin/mCherry fluorescence. Scale bars: 50 μm. d Quantification of single-cell pHi data collected as shown in (c). (N = 3 biological replicates; n = 91, 0.5% PEGDA; n = 90, 1% PEGDA; n = 102, 2% PEGDA; n = 89, 4% PEGDA. Red lines show medians ± IQR). e Representative images of H1299 cells stably expressing mCherry-pHluorin pH biosensor plated on varying Matrigel stiffnesses. Images show ratiometric display of pHluorin/mCherry fluorescence. Scale bars: 50 μm. f Quantification of single-cell pHi data collected as shown in (e). (N = 3 biological replicates; n = 93, 4 mg/mL; n = 92, 6 mg/mL; n = 102, 8 mg/mL; n = 97, 12 mg/mL. Red lines show medians ± IQR). For (d) and (f), significance was determined by a Kruskal-Wallis test (****P < 0.0001).

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