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Development of Polydimethylsiloxane Substrates with Tunable Elastic Modulus to Study Cell Mechanobiology in Muscle and Nerve

机译:具有可调弹性模量的聚二甲基硅氧烷基质的开发,以研究肌肉和神经的细胞力学生物学

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摘要

Mechanics is an important component in the regulation of cell shape, proliferation, migration and differentiation during normal homeostasis and disease states. Biomaterials that match the elastic modulus of soft tissues have been effective for studying this cell mechanobiology, but improvements are needed in order to investigate a wider range of physicochemical properties in a controlled manner. We hypothesized that polydimethylsiloxane (PDMS) blends could be used as the basis of a tunable system where the elastic modulus could be adjusted to match most types of soft tissue. To test this we formulated blends of two commercially available PDMS types, Sylgard 527 and Sylgard 184, which enabled us to fabricate substrates with an elastic modulus anywhere from 5 kPa up to 1.72 MPa. This is a three order-of-magnitude range of tunability, exceeding what is possible with other hydrogel and PDMS systems. Uniquely, the elastic modulus can be controlled independently of other materials properties including surface roughness, surface energy and the ability to functionalize the surface by protein adsorption and microcontact printing. For biological validation, PC12 (neuronal inducible-pheochromocytoma cell line) and C2C12 (muscle cell line) were used to demonstrate that these PDMS formulations support cell attachment and growth and that these substrates can be used to probe the mechanosensitivity of various cellular processes including neurite extension and muscle differentiation.
机译:在正常稳态和疾病状态下,力学是调节细胞形状,增殖,迁移和分化的重要组成部分。与软组织的弹性模量匹配的生物材料已经有效地研究了这种细胞的力学生物学,但是需要进行改进,以便以可控的方式研究更广泛的理化性质。我们假设聚二甲基硅氧烷(PDMS)共混物可以用作可调系统的基础,在该系统中可以调节弹性模量以匹配大多数类型的软组织。为了测试这一点,我们配制了两种市售PDMS类型的共混物Sylgard 527和Sylgard 184,这使我们能够制造弹性模量为5 kPa至1.72 MPa的基材。这是可调性的三个数量级范围,超过了其他水凝胶和PDMS系统所能达到的范围。独特地,可以独立于其他材料特性(包括表面粗糙度,表面能以及通过蛋白质吸附和微接触印刷使表面功能化的能力)来控制弹性模量。为了进行生物学验证,使用了PC12(神经诱导性嗜铬细胞瘤细胞系)和C2C12(肌肉细胞系)来证明这些PDMS制剂支持细胞附着和生长,并且这些底物可用于探测包括神经突在内的各种细胞过程的机械敏感性。伸展和肌肉分化。

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