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弹性纤维和网络在张力下的酶消化动力学。

Dynamics of enzymatic digestion of elastic fibers and networks under tension.

机构信息

Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.

出版信息

Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9414-9. doi: 10.1073/pnas.1019188108. Epub 2011 May 23.

Abstract

We study the enzymatic degradation of an elastic fiber under tension using an anisotropic random-walk model coupled with binding-unbinding reactions that weaken the fiber. The fiber is represented by a chain of elastic springs in series along which enzyme molecules can diffuse. Numerical simulations show that the fiber stiffness decreases exponentially with two distinct regimes. The time constant of the first regime decreases with increasing tension. Using a mean field calculation, we partition the time constant into geometrical, chemical and externally controllable factors, which is corroborated by the simulations. We incorporate the fiber model into a multiscale network model of the extracellular matrix and find that network effects do not mask the exponential decay of stiffness at the fiber level. To test these predictions, we measure the force relaxation of elastin sheets stretched to 20% uniaxial strain in the presence of elastase. The decay of force is exponential and the time constant is proportional to the inverse of enzyme concentration in agreement with model predictions. Furthermore, the fragment mass released into the bath during digestion is linearly related to enzyme concentration that is also borne out in the model. We conclude that in the complex extracellular matrix, feedback between the local rate of fiber digestion and the force the fiber carries acts to attenuate any spatial heterogeneity of digestion such that molecular processes manifest directly at the macroscale. Our findings can help better understand remodeling processes during development or in disease in which enzyme concentrations and/or mechanical forces become abnormal.

摘要

我们研究了在张力作用下弹性纤维的酶解降解,使用了各向异性的随机行走模型,并结合了削弱纤维的结合-解缚反应。纤维由一系列沿其扩散的弹性弹簧串联而成。数值模拟表明,纤维的刚度随两个不同的状态呈指数下降。第一个状态的时间常数随张力的增加而减小。使用平均场计算,我们将时间常数划分为几何、化学和外部可控因素,这与模拟结果相符。我们将纤维模型纳入细胞外基质的多尺度网络模型中,发现网络效应不会掩盖纤维水平上刚度的指数衰减。为了验证这些预测,我们测量了弹性蛋白片在弹性蛋白酶存在下拉伸至 20%单轴应变时的力松弛。力的衰减呈指数衰减,时间常数与酶浓度的倒数成正比,这与模型预测一致。此外,在消化过程中释放到浴中的片段质量与酶浓度呈线性关系,这在模型中也得到了证实。我们得出结论,在复杂的细胞外基质中,纤维消化的局部速率和纤维承载的力之间的反馈作用会削弱消化的任何空间异质性,从而使分子过程在宏观尺度上直接显现。我们的发现可以帮助更好地理解发育过程或疾病中的重塑过程,其中酶浓度和/或机械力变得异常。

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Dynamics of enzymatic digestion of elastic fibers and networks under tension.弹性纤维和网络在张力下的酶消化动力学。
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