Motahareh Mirzadeh

Master student

Effect of Matrix Stiffness on Angiogenesis and Proliferation in 3D Bioprinted Tumor Models

Supervisors: Prof. Aldo R. Boccaccini, Dr. Annika Kengelbach-Weigand (UKER), and Dr. Rafael Schmid (UKER)

This project investigates how variations in extracellular matrix (ECM) stiffness influence angiogenesis and tumor cell proliferation in engineered three-dimensional tumor microenvironments. Tumor progression is frequently accompanied by ECM remodelling that increases tissue stiffness, which in turn modulates cellular mechanotransduction pathways that affect proliferation and endothelial responses. Recent experimental evidence shows that matrix stiffening significantly enhances lymphatic endothelial cell proliferation and migration, indicating that stiffness contributes to the formation and expansion of vascular networks within the tumor microenvironment [1]. In parallel, in vitro studies demonstrate that ECM stiffness is sensed by cancer cells via integrin-mediated focal adhesion signalling, thereby activating downstream regulators such as FAK and ERK, which are associated with increased proliferative capacity in breast and other cancer cells, linking mechanical cues to oncogenic signalling [2].

To systematically explore these effects, this project will employ stiffness-tunable hydrogels and biofabricated matrices with controlled mechanical properties to culture both endothelial and cancer cells. By comparing cell behavior across stiffness regimes spanning physiological to pathological moduli, we aim to quantify how mechanical properties influence endothelial sprouting, vascular organization, and tumor proliferation in a three-dimensional context. Cellular outcomes will be assessed using quantitative imaging and proliferation assays, and mechanotransduction pathways will be analyzed to identify stiffness-dependent regulatory mechanisms. Understanding the interplay between ECM stiffness, angiogenic behavior, and tumor growth has important implications for the design of physiologically relevant in vitro models that more accurately recapitulate tumor mechanics and vascular interaction and can help identify stiffness-related mechanobiological targets for therapeutic intervention.

  1. Xu Z, Yu J, Chen D, Liu Y, Zhang G, Guo Q, Yang C, Gao F, He Y and Du Y, Extracellular matrix stiffness regulates the proliferation and migration capacities of lymphatic endothelial cells via FAT1. Front. Cell Dev. Biol. 13 (2025) 1667154. https://doi.org/10.3389/fcell.2025.1667154
  2. Jahin I., et al., Extracellular matrix stiffness activates mechanosensitive signals and modulates cancer cell proliferation and invasion, Front. Cell Dev. Biol. (2023). https://doi.org/10.3389/fcell.2023.1292775