Jesudason Rajiv, Black Lauren, Majumdar Arnab, Stone Phillip, Suki Bela
Department of Biomedical Engineering, Boston University, 44 Cummington St., Boston, MA 02215, USA.
J Appl Physiol (1985). 2007 Sep;103(3):803-11. doi: 10.1152/japplphysiol.00057.2007. Epub 2007 May 31.
Enzyme activity plays an essential role in many physiological processes and diseases such as pulmonary emphysema. While the lung is constantly exposed to cyclic stretching, the effects of stretch on the mechanical properties of the extracellular matrix (ECM) during digestion have not been determined. We measured the mechanical and failure properties of elastin-rich ECM sheets loaded with static or cyclic uniaxial stretch (40% peak strain) during elastase digestion. Quasistatic stress-strain measurements were taken during 30 min of digestion. The incremental stiffness of the sheets decreased exponentially with time during digestion. However, digestion in the presence of static stretch resulted in an accelerated stiffness decrease, with a time constant that was nearly 3 x smaller (7.1 min) than during digestion alone (18.4 min). These results were supported by simulations that used a nonlinear spring network model. The reduction in stiffness was larger during static than cyclic stretch, and the latter also depended on the frequency. Stretching at 20 cycles/min decreased stiffness less than stretching at 5 cycles/min, suggesting a rate-dependent coupling between mechanical forces and enzyme activity. Furthermore, pure digestion reduced the failure stress of the sheets from 88 +/- 21 kPa in control to 29 +/- 15 kPa (P < 0.05), while static and cyclic stretch resulted in a failure stress of 7 +/- 5 kPa (P < 0.05). We conclude that not only the presence but the dynamic nature of mechanical forces have a significant impact on enzyme activity, hence the deterioration of the functional properties of the ECM during exposure to enzymes.
酶活性在许多生理过程和疾病（如肺气肿）中起着至关重要的作用。虽然肺不断受到周期性拉伸，但在消化过程中拉伸对细胞外基质（ECM）机械性能的影响尚未确定。我们测量了在弹性蛋白酶消化过程中加载静态或周期性单轴拉伸（峰值应变40%）的富含弹性蛋白的ECM片材的机械性能和破坏性能。在消化30分钟期间进行准静态应力-应变测量。在消化过程中，片材的增量刚度随时间呈指数下降。然而，在静态拉伸存在下的消化导致刚度下降加速，其时间常数比单独消化时（18.4分钟）小近3倍（7.1分钟）。这些结果得到了使用非线性弹簧网络模型的模拟的支持。静态拉伸期间的刚度降低比循环拉伸期间更大，并且后者也取决于频率。以20次/分钟的频率拉伸比以5次/分钟的频率拉伸导致的刚度降低更小，这表明机械力和酶活性之间存在速率依赖性耦合。此外，单纯消化使片材的破坏应力从对照中的88±21 kPa降低到29±15 kPa（P<0.05），而静态和循环拉伸导致破坏应力为7±5 kPa（P<0.05）。我们得出结论，不仅机械力的存在，而且其动态性质对酶活性都有显著影响，因此在暴露于酶的过程中ECM功能特性会恶化。
