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Chemo-Mechanical Modulation of Cell Motions Using DNA Nanosprings
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2021-01-21 , DOI: 10.1021/acs.bioconjchem.0c00674 Deepak Karna 1 , Morgan Stilgenbauer 1 , Sagun Jonchhe 1 , Kazuya Ankai 2 , Ibuki Kawamata 3, 4 , Yunxi Cui 1, 5 , Yao-Rong Zheng 1 , Yuki Suzuki 2, 3 , Hanbin Mao 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2021-01-21 , DOI: 10.1021/acs.bioconjchem.0c00674 Deepak Karna 1 , Morgan Stilgenbauer 1 , Sagun Jonchhe 1 , Kazuya Ankai 2 , Ibuki Kawamata 3, 4 , Yunxi Cui 1, 5 , Yao-Rong Zheng 1 , Yuki Suzuki 2, 3 , Hanbin Mao 1
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Cell motions such as migration and change in cellular morphology are essential activities for multicellular organism in response to environmental stimuli. These activities are a result of coordinated clustering/declustering of integrin molecules at the cell membrane. Here, we prepared DNA origami nanosprings to modulate cell motions by targeting the clustering of integrin molecules. Each nanospring was modified with arginyl-glycyl-aspartic acid (RGD) domains with a spacing such that when the nanospring is coiled, the RGD ligands trigger the clustering of integrin molecules, which changes cell motions. The coiling or uncoiling of the nanospring is controlled, respectively, by the formation or dissolution of an i-motif structure between neighboring piers in the DNA origami nanodevice. At slightly acidic pH (<6.5), the folding of the i-motif leads to the coiling of the nanospring, which inhibits the motion of HeLa cells. At neutrality (pH 7.4), the unfolding of the i-motif allows cells to resume mechanical movement as the nanospring becomes uncoiled. We anticipate that this pH-responsive DNA nanoassembly is valuable to inhibit the migration of metastatic cancer cells in acidic extracellular environment. Such a chemo-mechanical modulation provides a new mechanism for cells to mechanically respond to endogenous chemical cues.
中文翻译：
使用 DNA 纳米弹簧对细胞运动进行化学机械调节
细胞运动（例如迁移和细胞形态的变化）是多细胞生物响应环境刺激的基本活动。这些活性是细胞膜上整合素分子协调聚集/解聚的结果。在这里，我们制备了 DNA 折纸纳米弹簧，通过靶向整合素分子的聚集来调节细胞运动。每个纳米弹簧都用精氨酰-甘氨酰-天冬氨酸（RGD）结构域进行修饰，其间距使得当纳米弹簧卷曲时，RGD配体触发整联蛋白分子的聚集，从而改变细胞运动。纳米弹簧的卷绕或展开分别通过DNA折纸纳米装置中相邻桥墩之间i-基序结构的形成或溶解来控制。在弱酸性 pH (<6.5) 下，i-基序的折叠导致纳米弹簧卷曲，从而抑制 HeLa 细胞的运动。在中性（pH 7.4）下，当纳米弹簧展开时，i-基序的展开使细胞能够恢复机械运动。我们预计这种 pH 响应性 DNA 纳米组装体对于抑制酸性细胞外环境中转移性癌细胞的迁移很有价值。这种化学机械调节为细胞对内源性化学信号做出机械反应提供了一种新机制。
更新日期：2021-02-17
中文翻译：
使用 DNA 纳米弹簧对细胞运动进行化学机械调节
细胞运动（例如迁移和细胞形态的变化）是多细胞生物响应环境刺激的基本活动。这些活性是细胞膜上整合素分子协调聚集/解聚的结果。在这里，我们制备了 DNA 折纸纳米弹簧，通过靶向整合素分子的聚集来调节细胞运动。每个纳米弹簧都用精氨酰-甘氨酰-天冬氨酸（RGD）结构域进行修饰，其间距使得当纳米弹簧卷曲时，RGD配体触发整联蛋白分子的聚集，从而改变细胞运动。纳米弹簧的卷绕或展开分别通过DNA折纸纳米装置中相邻桥墩之间i-基序结构的形成或溶解来控制。在弱酸性 pH (<6.5) 下，i-基序的折叠导致纳米弹簧卷曲，从而抑制 HeLa 细胞的运动。在中性（pH 7.4）下，当纳米弹簧展开时，i-基序的展开使细胞能够恢复机械运动。我们预计这种 pH 响应性 DNA 纳米组装体对于抑制酸性细胞外环境中转移性癌细胞的迁移很有价值。这种化学机械调节为细胞对内源性化学信号做出机械反应提供了一种新机制。
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