Mechanical cues are delivered to resident cells by the extracellular matrix and play an important role in directing cell processes, ranging from embryonic development and cancer metastasis to stem cell differentiation. Recently, cellular responses to viscoelastic and elastic mechanical cues have been studied; however, questions remain as to how cells identify and transduce these cues differently. We present a synthetic cell culture substrate with viscoelastic properties based on thioester exchange chemistry that can be modulated in situ with the photoinitiated thiol-ene ‘click’ reaction. With this method, stress relaxation in thioester hydrogels with an average relaxation time of 740,000 s can be switched off in the presence of cells without change to the elastic modulus. NIH 3T3 fibroblasts, cultured for 48 h on viscoelastic compared to elastic thioester substrates, displayed increased cell area (660–560 μm²) and increased nuclear to cytoplasmic YAP/TAZ ratios (2.4 to 2.2) when cultured on elastic compared to viscoelastic hydrogels, respectively. Next, when the viscoelasticity was switched off after 24 h, the fibroblasts responded to this change and exhibited an average cell area of 540 μm², and nuclear to cytoplasmic YAP/TAZ ratio of 2.1, approaching that of the control elastic gels. Phototunable viscoelastic thioester hydrogels provide a tunable materials system to investigate time-dependent cellular responses to viscoelasticity and should prove useful for understanding the dynamics of mechanoresponsive cellular pathways.

机械提示通过细胞外基质传递到驻留细胞，并在指导细胞过程中发挥重要作用，这些过程从胚胎发育和癌症转移到干细胞分化不等。最近，已经研究了细胞对粘弹性和弹性机械提示的反应。然而，有关细胞如何以不同方式识别和转导这些线索的问题仍然存在。我们提出了一种基于硫酯交换化学的，具有粘弹性的合成细胞培养基质，可以原位调节与光引发的硫醇-烯“点击”反应。使用这种方法，可以在没有细胞弹性模量的情况下关闭平均松弛时间为740,000 s的硫酯水凝胶的应力松弛。NIH 3T3成纤维细胞相比，弹性硫酯底物培养48小时在粘弹性，显示增加的细胞区（660-560  μ中号²）和增加的核质YAP / TAZ比（2.4〜2.2）上培养弹性相比时粘弹性的水凝胶， 分别。接着，当粘弹性在24小时后关闭时，成纤维细胞响应这一变化并表现出540的平均细胞面积 μ米²，并且核与细胞质的YAP / TAZ之比为2.1，接近对照弹性凝胶。光可调粘弹性硫酯水凝胶提供了可调谐的材料系统，以研究时间依赖性细胞对粘弹性的反应，并应被证明对理解机械反应性细胞途径的动力学有用。