Design of azobenzene-bearing hydrogel with photoswitchable mechanics driven by photo-induced phase transition for in vitro disease modeling
Design of azobenzene-bearing hydrogel with photoswitchable mechanics driven by photo-induced phase transition for in vitro disease modeling
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DOI：
10.1016/j.actbio.2021.03.028
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发表时间：
2021-09-06
影响因子：
9.7
通讯作者：
Nakanishi, Jun
中科院分区：
文献类型：
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作者：
Homma, Kenta;Chang, Alice C.;Nakanishi, Jun
细胞外基质（ECM）的力学在许多生物事件中表现出变化。在疾病进展期间，例如癌症，由于胶原基质的交联或通过细胞分泌的酶的基质降解，发生基质硬化或软化。工程水凝胶已经成为一种主要的体外模型，以模拟疾病进展过程中的这种动态力学。虽然已经有各种各样的工程水凝胶，但很少有人能在相同的工作原理下同时提供硬化和软化性能。此外，为了模拟个体疾病进展，需要控制机械变化的动力学。为此，我们描述了一种光响应性水凝胶，其通过光诱导相变经历刚度变化。该水凝胶由偶氮苯丙烯酸酯单体（AzoAA）和N，N-二甲基丙烯酰胺（DMA）的共聚物组成。通过调节偶氮苯的用量，由于偶氮苯的光致异构化作用，该聚合物的相变行为仅在光照射下发生。在37 ℃下通过浊度测量证实了该相行为。此外，交联的聚（AzoAA-r-DMA）凝胶在紫外光或可见光光的光异构化作用下发生可逆的溶胀-去溶胀。此外，聚（AzoAA-r-DMA）片状凝胶在偶氮苯的不同异构化状态下表现出模量的变化。当MCF-7细胞在凝胶上培养时，不同时间点的硬化诱导了E-cadherin基因表达水平的不同反应。这不仅表明了细胞在疾病进展过程中对力学变化的适应性行为，还证明了我们的材料在体外疾病建模方面的潜力。重要性声明在癌症等疾病进展过程中，称为细胞外基质（ECM）的细胞微环境经历了刚度变化。水凝胶是交联聚合物的溶胀网络，已用于模拟ECM的这种动态机械环境。然而，很少有人能在相同的工作原理下同时提供硬化和软化性能。在此，我们制作了一种新型的光响应水凝胶与开关力学，激活光诱导的结构变化的聚合物链内的水凝胶。当乳腺癌细胞在我们的动态水凝胶上培养时，基因表达和形态学观察表明，细胞对刚度变化的反应是短暂的，而不是持续的。光响应水凝胶提供了用作患者特定疾病模型的可能性。(C)2021 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Mechanics of the extracellular matrix (ECM) exhibit changes during many biological events. During disease progression, such as cancer, matrix stiffening or softening occurs due to crosslinking of the collagen matrix or matrix degradation through cell-secreted enzymes. Engineered hydrogels have emerged as a prime in vitro model to mimic such dynamic mechanics during disease progression. Although there have been a variety of engineered hydrogels, few can offer both stiffening and softening properties under the same working principle. In addition, to model individual disease progression, it is desirable to control the kinetics of mechanical changes. To this end, we describe a photoresponsive hydrogel that undergoes stiffness changes by the photo-induced phase transition. The hydrogel was composed of a copolymer of azobenzene acrylate monomer (AzoAA) and N,N-dimethyl acrylamide (DMA). By tuning the amount of azobenzene, the phase transition behavior of this polymer occurs solely by light irradiation, because of the photoisomerization of azobenzene. This phase behavior was confirmed at 37 degrees C by turbidity measurements. In addition, the crosslinked poly(AzoAA-r-DMA) gel undergoes reversible swelling-deswelling upon photoisomerization by ultraviolet or visible light. Furthermore, the poly(AzoAA-r-DMA) sheet gels exhibited modulus changes at different isomerization states of azobenzene. When MCF-7 cells were cultured on the gels, stiffening at different timepoints induced varied responses in the gene expression levels of E-cadherin. Not only did this suggest an adaptive behavior of the cells against changes in mechanics during disease progression, this also demonstrated our material's potential towards in vitro disease modeling.Statement of significanceDuring disease progression such as cancer, cellular microenvironment called extracellular matrix (ECM) undergoes stiffness changes. Hydrogels, which are swollen network of crosslinked polymers, have been used to model such dynamic mechanical environment of the ECM. However, few could offer both stiffening and softening properties under the same working principle. Herein, we fabricated a novel photoresponsive hydrogel with switchable mechanics, activated by photo-induced structural change of the polymer chains within the hydrogel. When breast cancer cells were cultured on our dynamic hydrogels, gene expression and morphological observation suggested that cells react to changes in stiffness by a transient response, as opposed to a sustained one. The photoresponsive hydrogel offers possibility for use as a patient-specific model of diseases. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.