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bioRxiv · 10.1101/2023.02.24.529926

Tenascin-C activation of lung fibroblasts in a 3D synthetic lung extracellular matrix mimic

Kundu, A. N.·Dougan, C. E.·Mahmoud, S.·Kilic, A.·Panagiotou, A.·Irakoze, N.·Richbourg, N.·Peyton, S. R.
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Abstract

The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that contain the ECM composition and biomechanics of the lung to study these cell-matrix interactions in vitro. Here, we developed a synthetic, bioactive hydrogel that mimics the native lung modulus, and includes a representative distribution of the most abundant ECM peptide motifs responsible for integrin binding and matrix metalloproteinase (MMP)-mediated degradation in the lung, which promotes quiescence of human lung fibroblasts (HLFs). Stimulation with transforming growth factor {beta}1 (TGF-{beta}1), metastatic breast cancer conditioned media (CM), or tenascin-C activated these hydrogel-encapsulated HLFs in a manner reflective of their native in vivo responses. We propose this lung hydrogel platform as a tunable, synthetic approach to study the independent and combinatorial effects of ECM in regulating fibroblast quiescence and activation.

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Kundu, A. N., Dougan, C. E., Mahmoud, S., Kilic, A., Panagiotou, A., Irakoze, N., Richbourg, N., Peyton, S. R.. 2023-02-24. Tenascin-C activation of lung fibroblasts in a 3D synthetic lung extracellular matrix mimic. https://doi.org/10.1101/2023.02.24.529926

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