Zhang Bo, Powers Joseph D, McCulloch Andrew D, Chi Neil C
Department of Bioengineering, University of California San Diego, La Jolla, CA, United States.
Institute for Engineering in Medicine, University of California San Diego, La Jolla, CA, United States.
Front Physiol. 2023 Mar 7;14:1126111. doi: 10.3389/fphys.2023.1126111. eCollection 2023.
Mechanosignaling describes processes by which biomechanical stimuli are transduced into cellular responses. External biophysical forces can be transmitted structural protein networks that span from the cellular membrane to the cytoskeleton and the nucleus, where they can regulate gene expression through a series of biomechanical and/or biochemical mechanosensitive mechanisms, including chromatin remodeling, translocation of transcriptional regulators, and epigenetic factors. Striated muscle cells, including cardiac and skeletal muscle myocytes, utilize these nuclear mechanosignaling mechanisms to respond to changes in their intracellular and extracellular mechanical environment and mediate gene expression and cell remodeling. In this brief review, we highlight and discuss recent experimental work focused on the pathway of biomechanical stimulus propagation at the nucleus-cytoskeleton interface of striated muscles, and the mechanisms by which these pathways regulate gene regulation, muscle structure, and function. Furthermore, we discuss nuclear protein mutations that affect mechanosignaling function in human and animal models of cardiomyopathy. Furthermore, current open questions and future challenges in investigating striated muscle nuclear mechanosignaling are further discussed.
机械信号转导描述了生物力学刺激被转化为细胞反应的过程。外部生物物理力可以通过从细胞膜延伸到细胞骨架和细胞核的结构蛋白网络进行传递，在细胞核中，它们可以通过一系列生物力学和/或生化机械敏感机制来调节基因表达，这些机制包括染色质重塑、转录调节因子的易位以及表观遗传因子。横纹肌细胞，包括心肌细胞和骨骼肌细胞，利用这些核机械信号转导机制来响应细胞内和细胞外机械环境的变化，并介导基因表达和细胞重塑。在这篇简短的综述中，我们重点介绍并讨论了最近的实验工作，这些工作聚焦于横纹肌细胞核-细胞骨架界面处生物力学刺激传播的途径，以及这些途径调节基因调控、肌肉结构和功能的机制。此外，我们还讨论了影响心肌病人类和动物模型中机械信号转导功能的核蛋白突变。此外，还进一步讨论了研究横纹肌细胞核机械信号转导目前存在的开放性问题和未来挑战。
