Dynamics of enzymatic digestion of elastic fibers and networks under tension
Dynamics of enzymatic digestion of elastic fibers and networks under tension
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DOI：
10.1073/pnas.1019188108
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发表时间：
2011-06-07
影响因子：
11.1
通讯作者：
Suki, Bela
中科院分区：
文献类型：
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作者：
Araujo, Ascanio D.;Majumdar, Arnab;Suki, Bela
我们研究了酶降解的弹性纤维在张力下使用各向异性的随机行走模型结合绑定-解除绑定的反应，削弱了纤维。这种纤维由一串弹性弹簧组成，沿着这些弹簧，酶分子可以扩散。数值模拟表明，纤维刚度呈指数下降与两个不同的制度。第一种状态的时间常数随着张力的增加而减小。使用平均场计算，我们划分的时间常数为几何，化学和外部可控的因素，这是证实了模拟。我们将纤维模型的细胞外基质的多尺度网络模型，并发现网络效应不掩盖指数衰减的刚度在纤维水平。为了测试这些预测，我们测量了弹性蛋白酶的存在下拉伸到20%的单轴应变的弹性蛋白片的力松弛。力的衰减是指数的，并且时间常数与酶浓度的倒数成比例，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线性相关，这也在模型中得到证实。我们的结论是，在复杂的细胞外基质中，纤维消化的局部速率和纤维所携带的力之间的反馈作用于减弱消化的任何空间异质性，使得分子过程直接在宏观尺度上表现出来。我们的研究结果可以帮助更好地了解发育过程中或疾病中的重塑过程，其中酶浓度和/或机械力变得异常。
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.