Department of Pharmaceutical Sciences, The University of Texas at El Paso, El Paso, TX, USA.
Department of Medicine, Fibrosis Research Center, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
Methods Mol Biol. 2021;2299:227-236. doi: 10.1007/978-1-0716-1382-5_17.
Durotaxis is the phenomena of directed cell migration driven by gradients of extracellular matrix stiffness. Durotaxis has been recently involved in the development of fibrosis by promoting the recruitment of pathological fibroblasts to areas of established fibrosis, thus amplifying the fibrotic response. Here, we describe the fabrication of mechanically patterned hydrogels that can be used to investigate molecular mechanisms controlling durotaxis of fibroblasts and other cells with mechanosensing properties. This method effectively creates a stiffness gradient of 275 Pa/μm, mimicking the natural spatial stiffness variations we observed in fibrotic tissues from mouse models of fibrosis and human fibrotic diseases.
趋硬性是指细胞在细胞外基质硬度梯度的驱动下定向迁移的现象。趋硬性最近被牵涉到纤维化的发展过程中,通过促进病理成纤维细胞向已形成纤维化的区域募集,从而放大纤维化反应。在这里,我们描述了机械图案化水凝胶的制造方法,该方法可用于研究控制成纤维细胞趋硬性和具有机械敏感性的其他细胞的分子机制。该方法有效地创建了 275 Pa/μm 的刚度梯度,模拟了我们在纤维化小鼠模型和人类纤维化疾病的纤维化组织中观察到的自然空间刚度变化。