The fields of mechanobiology and biomechanics are advancing our understanding of the complex behavior of soft tissues across multiple scales. While traditional methods like in-vitro studies and mechanical testing remain vital, the significance of computational techniques is growing, particularly for analyzing soft tissue nonlinearity and inelasticity. A current challenge is linking tissue microstructure to its functional role. In this study, we combine generative microstructural topology modeling with finite element analysis to elucidate these mechanistic relationships. More specifically, we incorporate a novel topology extraction pipeline validated across various biological networks and imaging techniques into computational models of the Extracellular Matrix (ECM) represented as a Discrete Fiber Network (DFN). Variations in topological configurations are introduced, and a range of loading scenarios are simulated to delve into the constitutive origins of tissue nonlinearity. These microstructure-informed models hold the potential to substantially deepen our understanding of biological materials characterized by a multiscale structure.