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. 2019 Aug 17;19:905–915. doi: 10.1016/j.isci.2019.08.023

Figure 5.

Figure 5

Coiling in Recapitulated In Vivo Environments

(A) Schematic showing the heterogeneity observed in environments neighboring breast tumors. Fibers of varied diameters, lengths, orientations, and architectures are interfaced with stromal cells that combined together induce pro- and anti-invasive cell behavior. Inset shows scanning electron microscopic images of fibers deposited in varying configurations (Wang and Nain, 2014) that mimic the native environments including random and aligned configurations. Scale bars, 10 μm.

(B) Cell migration starts with first cells sensing the native environments. Biophysical sensing of fibers can be studied by providing controlled and repeatable fiber architectures (spacing, bundles, and individual fibers of varying curvature). On left are representative phase images of cells on controlled fiber networks (scale bars, 10 μm). Bundling of small-diameter fibers can recover coil width kinetics as that of a single large diameter.

(C) Coiling during cell migration along fibers. Representative images showing “balled-up” cell morphology during migration on (i) high-curvature 135-nm-diameter fiber and elongated, “spindle” morphology during migration on (ii) low-curvature 1,000-nm diameter fiber. Scale bars, 5 μm. Yellow arrows show simultaneous coiling on both sides of the cell. Comparison between coiling dynamics on a protrusion assay and migration assay for ~135-nm-diameter and ~1,000-nm-diameter fiber cases. Sample sizes for the protrusion assay are as follows: 135 nm, 117; 1,000 nm, 77; and for the migration assay are 135 nm, 65; 1,000 nm, 63. (iii) Maximum coil width during migration as a function of the fiber diameter. Sample sizes are as follows: 135 nm, 65; 450 nm, 50; 1,000 nm, 63; 2,000 nm, 61; 4,000 nm, 66.

(D) Representative phase images of coiling dynamics exhibited by non-tumorigenic MCF-10A and metastatic MDA-MB-231 show diminished coiling in non-tumorigenic cell lines. Scale bar, 10 μm. Sample sizes for MDA-MB-231 are as follows: 135 nm, 65; 450 nm, 50; 1,000 nm, 63. Sample sizes for MCF 10A are as follows: 135 nm, 23; 450 nm, 36; 1,000 nm, 20. Data are represented as mean ± SEM. ∗p < 0.05; ∗∗p < 0.01 and ∗∗∗p < 0.001.