Vaughan T J, Mullen C A, Verbruggen S W, McNamara L M
Biomedical Engineering, Biomechanics Research Centre (BMEC), National University of Ireland Galway, Galway, Ireland.
Biomech Model Mechanobiol. 2015 Aug;14(4):703-18. doi: 10.1007/s10237-014-0631-3. Epub 2014 Nov 16.
Load-induced fluid flow acts as an important biophysical signal for bone cell mechanotransduction in vivo, where the mechanical environment is thought to be monitored by integrin and primary cilia mechanoreceptors on the cell body. However, precisely how integrin- and primary cilia-based mechanosensors interact with the surrounding fluid flow stimulus and ultimately contribute to the biochemical response of bone cells within either the in vitro or in vivo environment remains poorly understood. In this study, we developed fluid-structure interaction models to characterise the deformation of integrin- and primary cilia-based mechanosensors in bone cells under fluid flow stimulation. Under in vitro fluid flow stimulation, these models predicted that integrin attachments on the cell-substrate interface were highly stimulated ε(eq) > 200,000 με, while the presence of a primary cilium on the cell also resulted in significant strain amplifications, arising at the ciliary base. As such, these mechanosensors likely play a role in mediating bone mechanotransduction in vitro. Under in vivo fluid flow stimulation, integrin attachments along the canalicular wall were highly stimulated and likely play a role in mediating cellular responses in vivo. The role of the primary cilium as a flow sensor in vivo depended upon its configuration within the lacunar cavity. Specifically, our results showed that a short free-standing primary cilium could not effectively fulfil a flow sensing role in vivo. However, a primary cilium that discretely attaches the lacunar wall can be highly stimulated, due to hydrodynamic pressure in the lacunocanalicular system and, as such, could play a role in mediating bone mechanotransduction in vivo.
负荷诱导的流体流动在体内作为骨细胞机械转导的重要生物物理信号，其中机械环境被认为是由细胞体上的整合素和初级纤毛机械感受器监测的。然而，整合素和基于初级纤毛的机械传感器究竟如何与周围的流体流动刺激相互作用，并最终在体外或体内环境中对骨细胞的生化反应产生影响，目前仍知之甚少。在本研究中，我们开发了流固相互作用模型，以表征流体流动刺激下骨细胞中基于整合素和初级纤毛的机械传感器的变形。在体外流体流动刺激下，这些模型预测，细胞-基质界面上的整合素附着受到高度刺激（ε(eq)>200,000 με），而细胞上初级纤毛的存在也导致了在纤毛基部出现显著的应变放大。因此，这些机械传感器可能在体外介导骨机械转导中发挥作用。在体内流体流动刺激下，沿骨小管壁的整合素附着受到高度刺激，并可能在介导体内细胞反应中发挥作用。初级纤毛作为体内流动传感器的作用取决于其在腔隙内的构型。具体而言，我们的结果表明，短的独立初级纤毛在体内不能有效地发挥流动传感作用。然而，由于腔隙-骨小管系统中的流体动力压力，离散附着在腔隙壁上的初级纤毛可以受到高度刺激，因此可以在介导体内骨机械转导中发挥作用。
