Macrorheology and adaptive microrheology of endothelial cells subjected to fluid shear stress

Macrorheology and adaptive microrheology of endothelial cells subjected to fluid shear stress
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DOI:
10.1152/ajpcell.00193.2007
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发表时间:
2007-11-01
影响因子:
5.5
通讯作者:
Butler, Peter J.
Butler, Peter J.
中科院分区:
生物学2区
文献类型:
--
作者:
Dangaria, Jhanvi H.;Butler, Peter J.

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血管内皮细胞(ECs)通过改变其对白细胞的粘附性、血管扩张剂的分泌和对血源性成分的渗透性来响应血流动力学的时空特征。这些生理和病理生理变化与细胞力学和机械转导的适应有关,这是细胞将力转化为细胞内生化信号的过程。然而,这些机械适应的确切时间尺度仍然未知。我们使用颗粒跟踪微流变学来研究细胞内力学对流体剪切应力阶跃变化的自适应变化,模拟了血流动力学力的快速时间和稳定特征。结果表明,剪切应力从0 dyn/cm(2)阶跃变化到10 dyn/cm(2)后,ECs的柔顺性在30 s内明显增强,剪切后4 min内粘弹性参数恢复,即使剪切应力保持不变。在ECs被剪切5min后,逐步将剪应力恢复到0 dyn/cm(2)不会导致任何进一步的流变适应。通过将蠕变函数拟合到线性粘弹性液体模型中,利用平均囊泡位移来确定随时间变化的细胞变形和宏观流变参数。剪切诱导变形的特征时间为3 s,幅度为50 nm。我们得出的结论是,ECs可以迅速适应剪切应力的力学性能,并且我们提供了ECs随时间变形的第一个宏观流变参数,用于生理强迫函数。这些研究提供了对动脉粥样硬化等病理的深入了解,这可能在EC力学中找到它们的起源。
Vascular endothelial cells (ECs) respond to temporal and spatial characteristics of hemodynamic forces by alterations in their adhesiveness to leukocytes, secretion of vasodilators, and permeability to blood-borne constituents. These physiological and pathophysiological changes are tied to adaptation of cell mechanics and mechanotransduction, the process by which cells convert forces to intracellular biochemical signals. The exact time scales of these mechanical adaptations, however, remain unknown. We used particle-tracking microrheology to study adaptive changes in intracellular mechanics in response to a step change in fluid shear stress, which simulates both rapid temporal and steady features of hemodynamic forces. Results indicate that ECs become significantly more compliant as early as 30 s after a step change in shear stress from 0 to 10 dyn/cm(2) followed by recovery of viscoelastic parameters within 4 min of shearing, even though shear stress was maintained. After ECs were sheared for 5 min, return of shear stress to 0 dyn/cm(2) in a stepwise manner did not result in any further rheological adaptation. Average vesicle displacements were used to determine time-dependent cell deformation and macrorheological parameters by fitting creep function to a linear viscoelastic liquid model. Characteristic time and magnitude for shear-induced deformation were 3 s and 50 nm, respectively. We conclude that ECs rapidly adapt their mechanical properties in response to shear stress, and we provide the first macrorheological parameters for time-dependent deformations of ECs to a physiological forcing function. Such studies provide insight into pathologies such as atherosclerosis, which may find their origins in EC mechanics.