矩阵和细胞骨张力门拉伸诱导的信号传递
Patrick K Jaeger1, Fabian S Passini1, Barbara Niederoest1
1University Hospital Balgrist, University of Zurich, Switzerland; Institute for Biomechanics, ETH Zurich, Switzerland.
Acta biomaterialia
|September 13, 2025
概括
这项研究表明,细胞外基质 (ECM) 和细胞力学如何控制肌细胞感知机械负荷. 一个新的模型显示,ECM沉积是细胞对伸展反应的关键,对肌健康至关重要.
科学领域:
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
- 生物材料科学 生物材料科学
背景情况:
- 细胞外矩阵 (ECM) 机械和细胞机械传导之间的相互作用对于组织稳态至关重要,但仍然不太了解.
- 肌疾病涉及ECM失调,机械负荷是主要的治疗策略,但细胞感应机制尚不清楚.
- 现有的体外模型往往缺乏生理学相关性,无法准确研究肌细胞机械感知.
研究的目的:
- 研究细胞外基质 (ECM) 沉积和机制如何调节肌纤维细胞中的机械转导.
- 开发和验证一个动态的体外原组织模型,模仿生理肌负荷和细胞反应.
- 阐明ECM-细胞骨集成在调解拉伸诱导的信号传递中的作用.
主要方法:
- 使用人类肌纤维细胞开发了一种动态原生组织模型.
- 采用活细胞成像来监测拉伸诱导的信号.
- 评估了ECM沉积 (依赖 Askorbic 酸),ECM交叉连接,细胞骨张力和细胞对齐对机械敏感性的影响.
主要成果:
- 亚酸依赖的ECM沉积对于原生组织成熟和恢复生理菌株的信号是必不可少的.
- 机械传导灵敏度显著增加,菌株值从孤立细胞的40%降至成熟原组织的5%左右.
- ECM完整性,ECM-细胞骨融合和细胞骨张力极大地影响机械敏感性,ECM损伤与信号发射发生相关.
结论:
- 开发的原生组织模型成功地复制了在本地肌组织中观察到的负载诱导的信号.
- 在肌细胞感知机械负荷时,ECM机制和ECM-细胞骨融合是基本的.
- 该模型为研究肌退化和修复机制提供了一个生理学上相关的平台.
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