Fig. 5
Matrix stiffness influences decision-making, cellular ATP:ADP ratio, and glucose uptake during confined migration. a, b Migration decision-making (a) and passing time into each branch (b) in 0 mM and 100 mM glycated collagen microtracks (n = 25, 27 cells for 0 mM, 100 mM). c Transmitted light images showing cell morphology and confocal reflectance images of microtrack structure as well as cell-induced track displacement in 7 μm microtracks (yellow lines show microtrack walls; red arrowheads show areas of matrix displacement around the cell body). d, e Quantification of cell elongation (d) and track displacement (e) for cells in the 7 μm track of 0 mM and 100 mM glycated collagen gels (n = 31, 29 cells for 0 mM, 100 mM). f Model predictions for energy requirements for migration into tracks of varying size with increasing cell stiffness. g Normalized PercevalHR heatmap and 2-NBDG heatmap of cells in matrices of varying stiffness following glycation. h, i Normalized PercevalHR ratio (n = 0 mM: 47, 30, 31; 100 mM: 49, 28, 29 cells for 15, 12, 7 μm tracks) (h) and 2-NBDG uptake (n = 0 mM: 96, 53, 59; 100 mM: 71, 46, 35 cells for 15, 12, 7 μm tracks) (i) with increasing confinement in collagen gels glycated with 0 mM or 100 mM ribose. Data shown as mean ± s.e.m. (a, h, i), or median ± interquartile range (box), 5th–95th percentiles (whiskers), and mean (+) (b, d, e); dashed lines show exponential fit; two-tailed Mann–Whitney test (b, d, e, h, i) and extra sum-of-squares F-test for comparing curves (h, i); *P < 0.05, n.s. = not significant. Scale bar, 15 μm
