Abstract：
Mechanical forces are of major importance in regulating vascular homeostasis by influencing endothelial cell behavior and functions. Adherens junctions are critical sites for mechanotransduction in endothelial cells. β-catenin, a component of adherens junctions and the canonical Wnt signaling pathway, plays a role in mechanoactivation. Evidence suggests that β-catenin is involved in flow sensing and responds to tensional forces, impacting junction dynamics. The mechanoregulation of β-catenin signaling is context-dependent, influenced by the type and duration of mechanical loads. In endothelial cells, β-catenin\'s nuclear translocation and signaling are influenced by shear stress and strain, affecting endothelial permeability. The study investigates how shear stress, strain, and surface topography impact adherens junction dynamics, regulate β-catenin localization, and influence endothelial barrier properties. Insight box Mechanical loads are potent regulators of endothelial functions through not completely elucidated mechanisms. Surface topography, wall shear stress and cyclic wall deformation contribute overlapping mechanical stimuli to which endothelial monolayer respond to adapt and maintain barrier functions. The use of custom developed flow chamber and bioreactor allows quantifying the response of mature human endothelial to well-defined wall shear stress and gradients of strain. Here, the mechanoregulation of β-catenin by substrate topography, wall shear stress, and cyclic stretch is analyzed and linked to the monolayer control of endothelial permeability.
摘要：
机械力通过影响内皮细胞的行为和功能在调节血管稳态方面具有重要意义。粘附连接是内皮细胞中机械转导的关键位点。β-连环蛋白，粘附连接的一个组成部分和典型的Wnt信号通路，在机械激活中起作用。有证据表明，β-catenin参与流量传感并响应张力，影响接头动力学。β-连环蛋白信号的机械调节是上下文相关的，受机械载荷的类型和持续时间的影响。在内皮细胞中，β-连环蛋白的核易位和信号传导受剪切应力和应变的影响，影响内皮通透性。这项研究调查了剪切应力，应变，和表面形貌影响粘附体连接动力学，调节β-连环蛋白定位，并影响内皮屏障特性。观察箱机械负荷通过未完全阐明的机制是内皮功能的有效调节剂。表面形貌,壁剪切应力和循环壁变形有助于重叠的机械刺激，内皮单层响应以适应和维持屏障功能。定制开发的流动室和生物反应器的使用允许量化成熟的人内皮对明确定义的壁剪切应力和应变梯度的响应。这里,底物形貌对β-连环蛋白的机械调节，墙体剪应力，分析和循环拉伸，并将其与内皮通透性的单层控制联系起来。
