Robinson Benjamin K, Cortes Ernesto, Rice Alistair J, Sarper Muge, Del Río Hernández Armando
Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Biol Open. 2016 Jun 15;5(6):875-82. doi: 10.1242/bio.017632.
Extracellular matrix (ECM) remodelling is integral to numerous physiological and pathological processes in biology, such as embryogenesis, wound healing, fibrosis and cancer. Until recently, most cellular studies have been conducted on 2D environments where mechanical cues significantly differ from physiologically relevant 3D environments, impacting cellular behaviour and masking the interpretation of cellular function in health and disease. We present an integrated methodology where cell-ECM interactions can be investigated in 3D environments via ECM remodelling. Monitoring and quantification of collagen-I structure in remodelled matrices, through designated algorithms, show that 3D matrices can be used to correlate remodelling with increased ECM stiffness observed in fibrosis. Pancreatic stellate cells (PSCs) are the key effectors of the stromal fibrosis associated to pancreatic cancer. We use PSCs to implement our methodology and demonstrate that PSC matrix remodelling capabilities depend on their contractile machinery and β1 integrin-mediated cell-ECM attachment.
细胞外基质（ECM）重塑是生物学中众多生理和病理过程所不可或缺的，如胚胎发育、伤口愈合、纤维化和癌症。直到最近，大多数细胞研究都是在二维环境中进行的，其中机械信号与生理相关的三维环境有显著差异，这会影响细胞行为，并掩盖对健康和疾病中细胞功能的解释。我们提出了一种综合方法，通过ECM重塑在三维环境中研究细胞与ECM的相互作用。通过指定算法对重塑基质中I型胶原蛋白结构进行监测和定量分析，结果表明三维基质可用于将重塑与纤维化中观察到的ECM硬度增加相关联。胰腺星状细胞（PSC）是与胰腺癌相关的基质纤维化的关键效应细胞。我们利用PSC来实施我们的方法，并证明PSC的基质重塑能力取决于其收缩机制和β1整合素介导的细胞与ECM的附着。
