Spatial Configurations of 3D Extracellular Matrix Collagen Density and Anisotropy Simultaneously Guide Angiogenesis
Fig 6
Tumor associated collagen signatures (TACS) differentially facilitate neovessel recruitment.
Microvessels were simulated to originate in the stroma of a tumor periphery (inset, orange). Microvessels grew within the periphery toward the tumor (inset, magenta), separated by a structural interface (inset, yellow). Alignment and density of the interface was varied to mimic various TACS. The interface comprised an isotropic collagen ODF (circle), or aligned ODFs (ellipses) running perpendicular or along interface. The interface density was either low or high. Representative Z projections of the interface and tumor region are presented at the bottom. High interface density reduced the length of microvessels that crossed into the field (TACS-1 interfaces). Interface alignment along the tumor (TACS-2) deflected vessels or trapped them within the interface, while alignment radiating from the tumor facilitated vascular invasion (TACS-3). Fibril alignment in TACS-3 nullified the effects of increased matrix density. 1 way ANOVA. ***: p<0.001 w.r.t. baseline.