We investigated the role of collagen fiber morphology and matrix stiffness on cancer cell migration using multiphoton polymerized scaffolds based on Second-Harmonic Generation (SHG) images of ovarian tumors. We replicated the respective collagen fiber architectures and constructed models representing normal stroma, high-risk tissue, benign tumors, and high-grade tumors. The primary finding is that cell–matrix interactions such as motility, cell spreading, f-actin alignment, focal adhesion, and cadherin expression are mainly determined by the fiber morphology to a larger extent than the initial cell type. Moreover, increased matrix stiffness resulted in enhanced motility and cytoskeletal alignment, consistent with a durotactic mechanism.
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