Kundu Aritra Nath, Dougan Carey E, Mahmoud Samar, Kilic Alara, Panagiotou Alexi, Irakoze Ninette, Richbourg Nathan, Peyton Shelly R
Department of Chemical Engineering, University of Massachusetts Amherst.
Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst.
bioRxiv. 2023 Mar 20:2023.02.24.529926. doi: 10.1101/2023.02.24.529926.
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 . 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 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.
肺细胞外基质（ECM）维持组织的结构完整性，并调节驻留成纤维细胞的表型和功能。肺转移性乳腺癌会改变这些细胞与ECM的相互作用，促进成纤维细胞活化。因此，需要一种具有生物指导作用的ECM模型，该模型包含肺的ECM组成和生物力学特性，以研究这些细胞与基质的相互作用。在此，我们开发了一种合成的生物活性水凝胶，它模拟天然肺的模量，并包含肺中负责整合素结合和基质金属蛋白酶（MMP）介导降解的最丰富的ECM肽基序的代表性分布，可促进人肺成纤维细胞（HLF）的静止。用转化生长因子β1（TGF-β1）、转移性乳腺癌条件培养基（CM）或腱生蛋白-C刺激，以反映其天然反应的方式激活了这些水凝胶包裹的HLF。我们提出这个肺水凝胶平台作为一种可调节的合成方法，用于研究ECM在调节成纤维细胞静止和活化中的独立和组合作用。
