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Manipulating the mechanics of extracellular matrix to study effects on the nucleus and its structure
Methods ( IF 4.2 ) Pub Date : 2019-03-01 , DOI: 10.1016/j.ymeth.2018.12.009
Yuntao Xia , Sangkyun Cho , Manasvita Vashisth , Irena L. Ivanovska , P.C. Dave P. Dingal , Dennis E. Discher

Tissues such as brain, muscle, and bone differ greatly not only in their biological functions but also in their mechanical properties. Brain is far softer than muscle while bone is the stiffest tissue. Stiffness of extracellular microenvironments affects fundamental cell biological processes such as polarization and DNA replication, which affect nuclear size, shape, and levels of nuclear proteins such as the lamins that modulate gene expression. Reductionist approaches have helped dissect the effects of matrix mechanics away from confounding biochemical signals. Here, we summarize materials and methods for synthesizing and characterizing soft and stiff synthetic hydrogels widely used for mechanobiological studies. Such gels are also easily made to mimic the mechanical heterogeneity of fibrotic tissues. We further describe a nano-thin collagen fiber system, which enables control of anisotropy in addition to stiffness. With the different systems, we illustrate the effects of matrix mechanics on nuclear size, shape, and proteins including the lamins.

中文翻译:

操纵细胞外基质的力学以研究对细胞核及其结构的影响

大脑、肌肉和骨骼等组织不仅在生物学功能上而且在机械性能上都存在很大差异。大脑远比肌肉柔软,而骨骼是最坚硬的组织。细胞外微环境的刚度会影响基本的细胞生物学过程,例如极化和 DNA 复制,这会影响核大小、形状和核蛋白(例如调节基因表达的核纤层蛋白)的水平。还原论方法有助于剖析矩阵力学的影响,使其远离混杂的生化信号。在这里,我们总结了用于合成和表征广泛用于机械生物学研究的软硬合成水凝胶的材料和方法。这种凝胶也很容易模拟纤维化组织的机械异质性。我们进一步描述了一种纳米薄胶原纤维系统,除了刚度之外,它还能够控制各向异性。通过不同的系统,我们说明了基质力学对核大小、形状和蛋白质(包括核纤层蛋白)的影响。
更新日期:2019-03-01
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