Photoresponsive Hydrogels with Photoswitchable Mechanical Properties Allow Time-Resolved Analysis of Cellular Responses to Matrix Stiffening.

Photoresponsive Hydrogels with Photoswitchable Mechanical Properties Allow Time-Resolved Analysis of Cellular Responses to Matrix Stiffening.
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具有光开关力学性能的光响应水凝胶允许对基质硬化的细胞响应进行时间分辨分析。

DOI:
10.1021/acsami.7b18302
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发表时间:
2018-03-07
影响因子:
9.5
通讯作者:
Wong LS
Wong LS
中科院分区:
材料科学2区
文献类型:
--
作者:
Lee IN;Dobre O;Richards D;Ballestrem C;Curran JM;Hunt JA;Richardson SM;Swift J;Wong LS

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由于细胞功能和表型可以通过周围基质的机械特性来指导,水凝胶已经成为细胞培养系统的重要平台,其特性可以通过外部刺激(例如二价阳离子、酶处理和pH)来调节。然而,这些刺激中的许多可以直接影响细胞行为,使得难以区分纯粹的机械信号传导事件。本研究报告了一种水凝胶的开发,该水凝胶包含可光转换的交联剂,该交联剂在用适当波长的光照射时可以可逆地改变其刚度。此外,本研究报告了骨髓来源的间充质干细胞(MSC)对这些水凝胶的反应,这些水凝胶通过蓝光照射系统地硬化。基质被证明是无细胞毒性的,至关重要的是,MSC不受蓝光照射的影响。细胞形态的时间分辨分析表明,响应于更大的基板刚度的特征细胞扩展和增加的纵横比。这种水凝胶提供了一个研究细胞中响应刚度动态变化的机械信号传导的平台,为研究机械转导信号传导途径和生物过程提供了一种新的方法,其中隐含了组织力学的变化,如发育,衰老和纤维化。
As cell function and phenotype can be directed by the mechanical characteristics of the surrounding matrix, hydrogels have become important platforms for cell culture systems, with properties that can be tuned by external stimuli, such as divalent cations, enzymatic treatment, and pH. However, many of these stimuli can directly affect cell behavior, making it difficult to distinguish purely mechanical signaling events. This study reports on the development of a hydrogel that incorporates photoswitchable cross-linkers, which can reversibly alter their stiffness upon irradiation with the appropriate wavelength of light. Furthermore, this study reports the response of bone-marrow-derived mesenchymal stem cells (MSCs) on these hydrogels that were stiffened systematically by irradiation with blue light. The substrates were shown to be noncytotoxic, and crucially MSCs were not affected by blue-light exposure. Time-resolved analysis of cell morphology showed characteristic cell spreading and increased aspect ratios in response to greater substrate stiffness. This hydrogel provides a platform to study mechanosignaling in cells responding to dynamic changes in stiffness, offering a new way to study mechanotransduction signaling pathways and biological processes, with implicit changes to tissue mechanics, such as development, ageing, and fibrosis.
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