Rapid responses of human pluripotent stem cells to cyclic mechanical strains applied to integrin by acoustic tweezing cytometry.
Rapid responses of human pluripotent stem cells to cyclic mechanical strains applied to integrin by acoustic tweezing cytometry.
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DOI：
10.1038/s41598-023-45397-5
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发表时间：
2023-10-21
影响因子：
4.6
通讯作者：
Deng, Cheri X.
中科院分区：
文献类型：
--
作者：
Xu, Zhaoyi;Liu, Shiying;Xue, Xufeng;Li, Weiping;Fu, Jianping;Deng, Cheri X.
声学镊子流式细胞术（ATC）是一种基于超声的生物物理技术，已显示出促进人类多能干细胞（hPSC）分化的能力。该研究系统地检查了hPSC如何响应ATC通过使用超声脉冲（声压0.034 MPa，中心频率1.24 MHz和脉冲重复频率1 Hz）置换整合素结合的微泡（平均直径4.3 µm）施加的循环机械应变。我们的数据显示，在分别应用ATC短至1分钟和5分钟后，hPSC中多能性标志物八聚体结合转录因子4（OCT 4）下调至少10%，并且Yes相关蛋白（雅普）的核定位增加几乎100%。ATC刺激下的整合素锚定的微泡的运动分析揭示了不同阶段的粘弹性特征行为和整合素-细胞骨架（CSK）连接的变形增加。当超声脉冲占空比从5%增加到50%或每个超声脉冲的持续时间从0.05增加到0.5 s时，整合素结合微泡的峰值位移从1.45 ± 0.16 μm增加到4.74 ± 0.67 μm。在ATC应用过程中实时跟踪整合素结合的微泡检测到微泡位移与hPSC中OCT 4下调的高度相关性。总之，我们的数据显示了hPSC中OCT 4响应ATC刺激的快速下调，突出了hPSC对整合素靶向的循环力/应变的独特机械敏感性，这取决于超声脉冲的脉冲持续时间或占空比，从而为ATC诱导的hPSC加速分化的机制提供了见解。
Acoustic tweezing cytometry (ATC) is an ultrasound-based biophysical technique that has shown the capability to promote differentiation of human pluripotent stem cells (hPSCs). This study systematically examined how hPSCs respond to cyclic mechanical strains applied by ATC via displacement of integrin-bound microbubbles (averaged diameter of 4.3 µm) using ultrasound pulses (acoustic pressure 0.034 MPa, center frequency 1.24 MHz and pulse repetition frequency 1 Hz). Our data show downregulation of pluripotency marker Octamer-binding transcription factor 4 (OCT4) by at least 10% and increased nuclear localization of Yes-associated protein (YAP) by almost 100% in hPSCs immediately after ATC application for as short as 1 min and 5 min respectively. Analysis of the movements of integrin-anchored microbubbles under ATC stimulations reveals different stages of viscoelastic characteristic behavior and increasing deformation of the integrin-cytoskeleton (CSK) linkage. The peak displacement of integrin-bound microbubbles increased from 1.45 ± 0.16 to 4.74 ± 0.67 μm as the duty cycle of ultrasound pulses increased from 5% to 50% or the duration of each ultrasound pulse increased from 0.05 to 0.5 s. Real-time tracking of integrin-bound microbubbles during ATC application detects high correlation of microbubble displacements with OCT4 downregulation in hPSCs. Together, our data showing fast downregulation of OCT4 in hPSCs in respond to ATC stimulations highlight the unique mechanosensitivity of hPSCs to integrin-targeted cyclic force/strain dependent on the pulse duration or duty cycle of ultrasound pulses, providing insights into the mechanism of ATC-induced accelerated differentiation of hPSCs.
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