Enríquez Ángel, Libring Sarah, Field Tyler C, Jimenez Julian, Lee Taeksang, Park Hyunsu, Satoski Douglas, Wendt Michael K, Calve Sarah, Tepole Adrian Buganza, Solorio Luis, Lee Hyowon
Weldon School of Biomedical Engineering, Birck Nanotechnology Center, Center for Implantable Devices, Purdue University, West Lafayette, IN 47907, USA.
Weldon School of Biomedical Engineering, Birck Nanotechnology Center, Purdue University, West Lafayette, IN 47907, USA.
Adv Funct Mater. 2021 Jan 4;31(1). doi: 10.1002/adfm.202005021. Epub 2020 Sep 23.
Accurately replicating and analyzing cellular responses to mechanical cues is vital for exploring metastatic disease progression. However, many of the existing platforms for applying mechanical stimulation seed cells on synthetic substrates. To better recapitulate physiological conditions, a novel actuating platform is developed with the ability to apply tensile strain on cells at various amplitudes and frequencies in a high-throughput multi-well culture plate using a physiologically-relevant substrate. Suspending fibrillar fibronectin across the body of the magnetic actuator provides a matrix representative of early metastasis for 3D cell culture that is not reliant on a synthetic substrate. This platform enables the culturing and analysis of various cell types in an environment that mimics the dynamic stretching of lung tissue during normal respiration. Metabolic activity, YAP activation, and morphology of breast cancer cells are analyzed within one week of cyclic stretching or static culture. Further, matrix degradation is significantly reduced in breast cancer cell lines with metastatic potential after actuation. These new findings demonstrate a clear suppressive cellular response due to cyclic stretching that has implications for a mechanical role in the dormancy and reactivation of disseminated breast cancer cells to macrometastases.
准确复制和分析细胞对机械信号的反应对于探索转移性疾病进展至关重要。然而，许多现有的施加机械刺激的平台是将细胞接种在合成基质上。为了更好地重现生理条件，开发了一种新型驱动平台，该平台能够在高通量多孔培养板中使用生理相关基质，以各种幅度和频率对细胞施加拉伸应变。在磁致动器主体上悬浮纤维状纤连蛋白，为三维细胞培养提供了一种代表早期转移的基质，这种基质不依赖于合成基质。该平台能够在模拟正常呼吸过程中肺组织动态拉伸的环境中培养和分析各种细胞类型。在循环拉伸或静态培养一周内，分析乳腺癌细胞的代谢活性、YAP激活和形态。此外，具有转移潜能的乳腺癌细胞系在驱动后基质降解显著减少。这些新发现表明，循环拉伸会引起明显的细胞抑制反应，这对机械作用在播散性乳腺癌细胞休眠和重新激活至大转移中的作用具有重要意义。
