Li Bohan, Fu Qingyu, Lu Yan, Chen Cheng, Zhao Yingshuai, Zhao Yuanfeng, Cao Minghui, Zhou Wei, Fan Xiaoliang, Jiang Xiaoyu, Zhao Peng, Zheng Yijun
School of Physical Science and Technology, ShanghaiTech University, Shanghai, China.
State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, China.
Nat Commun. 2025 May 24;16(1):4831. doi: 10.1038/s41467-025-60062-3.
Mechanical forces play a critical role in regulating cancer cell behavior, particularly during metastasis. Here we present a three-dimensional hydrogel platform embedded with near-infrared-responsive macromolecular actuators that enable precise mechanical stimulation of specific integrin subtypes in cancer cells. By leveraging this system, we investigate how different force parameters-magnitude, frequency, and duration-affect the migration and invasion of ovarian cancer cell spheroids, focusing on the integrins αvβ3 and αvβ6. We find that mechanical stimulation enhances collective invasion at early stages and triggers a mesenchymal-to-amoeboid transition during later migration, especially when high-frequency, large-amplitude forces disrupt αvβ3-ligand interactions. In contrast, cells engaging αvβ6-through higher-affinity binding-show limited transition under similar conditions. Molecular simulations support these findings by revealing the underlying mechanics of integrin-specific responses. This 3D hydrogel platform provides a powerful tool for studying mechanotransduction in cancer cells and offers potential insights for developing targeted cancer therapies.
机械力在调节癌细胞行为中起着关键作用，尤其是在转移过程中。在此，我们展示了一种三维水凝胶平台，其嵌入了近红外响应性大分子致动器，能够对癌细胞中的特定整合素亚型进行精确的机械刺激。通过利用该系统，我们研究了不同的力参数——大小、频率和持续时间——如何影响卵巢癌细胞球体的迁移和侵袭，重点关注整合素αvβ3和αvβ6。我们发现，机械刺激在早期增强集体侵袭，并在后期迁移过程中触发间充质到阿米巴样转变，特别是当高频、大幅度力破坏αvβ3-配体相互作用时。相比之下，通过更高亲和力结合参与αvβ6的细胞在类似条件下显示出有限的转变。分子模拟通过揭示整合素特异性反应的潜在机制支持了这些发现。这种三维水凝胶平台为研究癌细胞中的机械转导提供了一个强大的工具，并为开发靶向癌症治疗提供了潜在的见解。
