Friedland F, Babu S, Springer R, Konrad J, Herfs Y, Gerlach S, Gehlen J, Krause H-J, De Laporte L, Merkel R, Noetzel E
Institute of Biological Information Processing 2 (IBI-2): Mechanobiology, Forschungszentrum Jülich, Jülich, Germany.
DWI-Leibniz Institute for Interactive Materials, Aachen, Germany.
Front Cell Dev Biol. 2022 Aug 29;10:947430. doi: 10.3389/fcell.2022.947430. eCollection 2022.
Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells. MCF10A-derived breast acini with basement membranes (BM) of defined maturation state and basoapical polarization were used to resemble breast gland morphogenesis . The novel biophysical tool was used to apply cyclic shear strain with defined amplitudes (≤15%, 0.2 Hz) over 22 h on living spheroids embedded in an ultrasoft matrix (<60 Pa). We demonstrated that breast spheroids gain resistance to shear strain, which increased with BM maturation and basoapical polarization. Most intriguingly, poorly developed spheroids were prone to cyclic strain-induced extrusion of apoptotic cells from the spheroid body. In contrast, matured spheroids were insensitive to this mechanoresponse-indicating changing mechanosensing or mechanotransduction mechanisms during breast tissue morphogenesis. Together, we introduced a versatile tool to study cyclic shear stress responses of 3D cell culture models. It can be used to strain, in principle, all kinds of cell clusters, even those that grow only in ultrasoft hydrogels. We believe that this approach opens new doors to gain new insights into dynamic shear strain-induced mechanobiological regulation circuits between cells and their ECM.
人类乳腺上皮细胞会受到各种机械性细胞外基质（ECM）应力的影响，这些应力调节着组织的发育和内稳态。由于缺乏有效的实验方法，乳腺组织对ECM传递的剪切应力的机械适应一直未得到充分研究。因此，我们创建了一种磁剪切应变装置，首次能够分析人类乳腺细胞的即时剪切应变反应。使用具有确定成熟状态和基底-顶端极化的基底膜（BM）的MCF10A衍生乳腺腺泡来模拟乳腺形态发生。这种新型生物物理工具用于在嵌入超软基质（<60 Pa）的活球体上施加22小时、振幅确定（≤15%，0.2 Hz）的循环剪切应变。我们证明乳腺球体获得了对剪切应变的抗性，这种抗性随着BM成熟和基底-顶端极化而增加。最有趣的是，发育不良的球体容易因循环应变而导致凋亡细胞从球体主体挤出。相比之下，成熟的球体对这种机械反应不敏感，这表明在乳腺组织形态发生过程中机械传感或机械转导机制发生了变化。总之，我们引入了一种通用工具来研究3D细胞培养模型的循环剪切应力反应。原则上，它可用于对各种细胞簇施加应变，甚至是那些仅在超软水凝胶中生长的细胞簇。我们相信这种方法为深入了解动态剪切应变诱导的细胞与其ECM之间的机械生物学调节回路打开了新的大门。
