Figure 4

Microtissues develop community structure through selective functional remodeling. (A) Overall modularity of microtissues significantly increased (p = 0.046) at week 3 and remained increased (p = 0.0475) at week 4. (B) Representative image of the physical layout of module nodes. Module 1 nodes (red dots) and their intra-modular connections (orange lines) are physically interspersed with module 2 nodes (blue dots) and their intra-modular connections (light blue lines). (C) Number of modules present in microtissues does not change over the first 4 weeks of development. (D) The intra-module correlation is not significantly different (p = 0.0834) from the inter-module correlation in week 2. In weeks 3 and 4 the intra- and inter- module correlations significantly separated (week 3, p = 0.0045; week 4, p < 0.0001). (E) Schematics of community structure formation based on data from (D), with intra-modular connections in red (module 1) or blue (module 2), and inter-module connections in magenta. Week 2 reflects that there was no difference between the intra-module and inter-module connections. The week 3 schematic depicts the overall decrease in functional connectivity, which disproportionately affects inter-module connection. The week 4 schematic shows the overall increase in connectivity, with an increase in intra-module connections and a decrease in inter-module connections. (F) There is little correlation between module size (number of nodes) and the intra-module correlation at week 2 and week 3. At week 4 there is a small positive correlation between module size and average correlation, indicating that large modules in week 4 were functionally more connected. Significance for modularity and number of modules across multiple weeks were determined with a one-way ANOVA and post-hoc Tukey test with p < 0.05 (*p < 0.05). Significance between intra-modular and inter-modular correlations were determined with unpaired, two tailed t-tests with p < 0.05 (**p < 0.01, ***p < 0.001, ****p < 0.0001).