交联肌动蛋白网络中钙调蛋白稳定化的微观结构模型
Microstructural model for calponin stabilization of crosslinked actin networks
摘要:
人工合成的肌动蛋白网络由于其柔软和湿润的性质,模仿许多生物支架结构,作为生物材料需要极大的兴趣。对这些结构的研究有助于更好地理解这种新的微/纳米技术和细胞骨架样结构构建块。在细胞内,肌动蛋白网络受到数十种肌动蛋白结合蛋白(ABP)的调节,这使得一个高度复杂系统具有多种涌现行为。特别是钙调蛋白是一种ABP,被鉴定为肌动蛋白稳定剂,但其机制知之甚少。最近的实验使用的体外模型系统的交联肌动蛋白与钙调蛋白和大变形体流变学,发现网络与碱性钙调蛋白表现出延迟的发病,并能够承受更高的最大应变软化前。在这项工作中,我们提出了一个数学模型到非线性连续介质力学的框架来解释詹森的观察,在那里我们引入的假设,这两个网络之间的差异,有和没有钙调蛋白,被解释为一个改变的预应变开发的网络纠缠和调节的交联粘附能。的F-肌动蛋白的力学建模使用蠕虫状链模型的半柔性长丝和凝胶化过程被描述为介观动力学的交联。该模型已与文献报道的实验结果进行了验证,显示出良好的理论和实验之间的协议。
英文摘要:
The synthetic actin network demands great interest as bio-material due to its soft and wet nature that mimic many biological scaffolding structures. The study of these structures can contribute to a better understanding of this new micro/nano technology and the cytoskeleton like structural building blocks. Inside the cell the actin network is regulated by tens of actin-binding proteins (ABP's), which makes for a highly complex system with several emergent behavior. In particular Calponin is an ABP that was identified as an actin stabiliser, but its mechanism is poorly understood. Recent experiments using an in vitro model system of cross-linked actin with Calponin and large deformation bulk rheology, found that networks with basic calponin exhibited a delayed onset and were able to withstand a higher maximal strain before softening. In this work we propose a mathematical model into the framework of nonlinear continuum mechanics to explain the observation of Jansen, where we introduce the hypothesis by which the difference between the two networks, with and without Calponin, is interpreted as a alterations in the pre-strain developed by the network entanglement and the regulation of the crosslinks adhesion energy. The mechanics of the F-actin is modelled using the wormlike chain model for semi-flexible filaments and the gelation process is described as mesoscale dynamics for the crosslinks. The model has been validated with reported experimental results from literature, showing a good agreement between theory and experiments.
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