Fig. 4: Representative simulations (top) of the time course of filopodia activity for four stiffnesses, depicting distinct patterning behaviors in the biphasic patterning response, with relative interpretations for vascular network formation (bottom⁵⁰).

The color scheme is representative of the cellular filopodia activity, tip cells indicated with bright green and stalk cells indicated in purple. a Relatively low stiffness (1.5 kPa) causes slow patterning, low filopodia activity and therefore sparse network formation. b Stiffness equal to 9.8 kPa induces fast patterning and intermediate filopodia activity, resulting in physiological network formation. c Relatively high stiffness (17 kPa) causes slow patterning but with high filopodia activity pre-patterning and, therefore, dense and malformed network formation. d Very high stiffness levels (400 kPa) do not induce tip/stalk patterning and induce generally high filopodia activity. The red lines indicate the timepoint of pattern formation. The schematics were created using BioRender.