The Synergistic Regulation of Lung Cancer Cell Migration by Tensile Stress and Matrix Stiffness.

IF 3.5 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2026-05-25 eCollection Date: 2026-06-01 DOI:10.1007/s12195-026-00914-0

Yii-Chun Chen, Shuai Shao, Xiaohui Yu, Chao Guo, Daqing Wang, Hangyu Zhang, Bo Liu

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引用次数: 0

Abstract

Purpose: To investigate the synergistic effects of matrix stiffness and cyclic tensile stress-key mechanical cues in the lung tumor microenvironment-on lung cancer cell migration, and to elucidate the underlying mechanotransduction pathways.

Methods: A novel cell-stretch coupling device was developed by integrating tunable P(SBMA-co-AAm) hydrogels (8.9, 49.4, and 99.5 kPa) with stretchable PDMS chambers via an interpenetrating polymer network. A549 lung cancer cells expressing FRET-based biosensors for FAK, Src, and RhoGDI α were subjected to cyclic stretching (10 or 20% strain, 1 Hz). Inhibitors (PF228 for FAK, PP1 for Src, ML-7 for cytoskeleton) were used to dissect signaling pathways.

Results: On soft and medium-stiffness substrates (8.9-49.4 kPa), cyclic stretching significantly enhanced cell migration (by 22.5-38.7%) and activated FAK/Src while suppressing RhoGDI α. High stiffness (99.5 kPa) rendered cells unresponsive to stretch (≤ 3.2% change). FAK and Src jointly regulated RhoGDI α, with FAK dominance under low stiffness. Cytoskeletal inhibition abolished mechanoresponses, confirming its role as a central mechanosensor.

Conclusion: The study establishes a biomimetic platform for dual mechanical stimulation and reveals stiffness-dependent synergy between tensile stress and matrix stiffness in promoting lung cancer migration via the FAK/Src-RhoGDI α axis. These findings provide mechanistic insights into mechanotransduction in lung cancer and suggest potential targets for inhibiting metastasis by disrupting mechanical signaling.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-026-00914-0.

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拉应力和基质刚度对肺癌细胞迁移的协同调节。

目的：探讨肺肿瘤微环境中基质刚度和循环拉伸应力的协同作用对肺癌细胞迁移的影响，并阐明其潜在的机械转导途径。方法：通过互穿聚合物网络将可调P（SBMA-co-AAm）水凝胶（8.9、49.4和99.5 kPa）与可拉伸的PDMS腔体集成，开发了一种新型细胞拉伸耦合装置。表达FAK、Src和RhoGDI α基于fret的生物传感器的A549肺癌细胞进行循环拉伸（10%或20%应变，1 Hz）。抑制剂（PF228用于FAK， PP1用于Src， ML-7用于细胞骨架）用于解剖信号通路。结果：在软性和中等刚度底物（8.9-49.4 kPa）上，循环拉伸显著增强细胞迁移（22.5-38.7%），激活FAK/Src，同时抑制RhoGDI α。高刚度（99.5 kPa）使细胞对拉伸无反应（≤3.2%的变化）。FAK和Src共同调控RhoGDI α，在低刚度下FAK占优势。细胞骨架抑制消除机械反应，确认其作为中心机械传感器的作用。结论：本研究建立了双重机械刺激的仿生平台，揭示了拉伸应力和基质刚度之间通过FAK/Src-RhoGDI α轴促进肺癌迁移的刚度依赖协同作用。这些发现为肺癌的机械转导提供了机制上的见解，并提出了通过破坏机械信号来抑制转移的潜在靶点。补充信息：在线版本包含补充资料，下载地址为10.1007/s12195-026-00914-0。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.