Tenascin-C activation of lung fibroblasts in a 3D synthetic lung extracellular matrix mimic
Year: 2023
Type: preprint
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 β1 (TGF-β1), 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.
Authors: Aritra Nath Kundu, Carey E. Dougan, Samar Mahmoud, Alara Kilic, Alexi Panagiotou, Ninette Irakoze, Nathan Richbourg, Shelly R. Peyton
Institution: University of Massachusetts Amherst
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: green
Awards: G3104905749, Acquisition of an Orbitrap MS, G3563128861, CAREER: Mechanisms of Drug Resistance in a Responsive Biomaterial Platform, Tissue-specific stem cells and breast cancer tissue tropism, Chemistry Biology Interface Predoctoral Training Grant, G6671297155, G6711204355, G7578039057, Biotechnology Training Program in Applied Life Sciences
OpenAlex ID: W4322008791