Raha Arjun, Wu Yuning, Zhong Lily, Raveenthiran Jatheeshan, Hong Minji, Taiyab Aftab, Wang Li, Wang Bill, Geng Fei
School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada.
Integrated Biomedical Engineering and Health Sciences Program, McMaster University, Hamilton, ON, Canada.
Mol Brain. 2023 Dec 20;16(1):83. doi: 10.1186/s13041-023-01071-5.
Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet the underlying mechanistic model of signaling pathways in brain mechanotransduction remains enigmatic. To bridge this gap, we introduced an in situ multi-scale platform, through which we delineate comprehensive brain biomechanical traits in white matter (WM), grey-white matter junctions (GW junction), and the pons across human brain tissue from four distinct donors. We investigate the three-dimensional expression patterns of Piezo1, Piezo2, and TMEM150C, while also examining their associated histological features and mechanotransduction signaling networks, particularly focusing on the YAP/β-catenin axis. Our results showed that the biomechanical characteristics (including stiffness, spring term, and equilibrium stress) associated with Piezo1 vary depending on the specific region. Moving beyond Piezo1, our result demonstrated the significant positive correlations between Piezo2 expression and stiffness in the WM. Meanwhile, the expression of Piezo2 and TMEM150C was shown to be correlated to viscoelastic properties in the pons and WM. Given the heterogeneity of brain tissue, we investigated the three-dimensional expression of Piezo1, Piezo2, and TMEM150C. Our results suggested that three mechanosensitive proteins remained consistent across different vertical planes within the tissue sections. Our findings not only establish Piezo1, Piezo2, and TMEM150C as pivotal mechanosensors that regulate the region-specific mechanotransduction activities but also unveil the paradigm connecting brain mechanical properties and mechanotransduction activities and the variations between individuals.
揭示机械因素与大脑活动之间的复杂关系是一项关键任务，然而大脑机械转导中信号通路的潜在机制模型仍然神秘莫测。为了填补这一空白，我们引入了一个原位多尺度平台，通过该平台描绘了来自四个不同供体的人脑组织中白质（WM）、灰白质交界处（GW交界处）和脑桥的综合脑生物力学特征。我们研究了Piezo1、Piezo2和TMEM150C的三维表达模式，同时还检查了它们相关的组织学特征和机械转导信号网络，特别关注YAP/β-连环蛋白轴。我们的结果表明，与Piezo1相关的生物力学特征（包括刚度、弹性项和平衡应力）因特定区域而异。除了Piezo1之外，我们的结果还表明Piezo2表达与WM中的刚度之间存在显著正相关。同时，Piezo2和TMEM150C的表达与脑桥和WM中的粘弹性特性相关。鉴于脑组织的异质性，我们研究了Piezo1、Piezo2和TMEM150C的三维表达。我们的结果表明，三种机械敏感蛋白在组织切片内的不同垂直平面上保持一致。我们的发现不仅将Piezo1、Piezo2和TMEM150C确立为调节区域特异性机械转导活动的关键机械传感器，还揭示了连接脑机械特性和机械转导活动的范式以及个体之间的差异。
