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Matrix degradation regulates osteoblast protrusion dynamics and individual migration.
Integrative Biology ( IF 1.5 ) Pub Date : 2020-01-10 , DOI: 10.1093/intbio/zyz035
Nieves Movilla 1 , Clara Valero 1 , Carlos Borau 1 , Jose Manuel García-Aznar 1
Affiliation  

Protrusions are one of the structures that cells use to sense their surrounding environment in a probing and exploratory manner as well as to communicate with other cells. In particular, osteoblasts embedded within a 3D matrix tend to originate a large number of protrusions compared to other type of cells. In this work, we study the role that mechanochemical properties of the extracellular matrix (ECM) play on the dynamics of these protrusions, namely, the regulation of the size and number of emanating structures. In addition, we also determine how the dynamics of the protrusions may lead the 3D movement of the osteoblasts. Significant differences were found in protrusion size and cell velocity, when degradation activity due to metalloproteases was blocked by means of an artificial broad-spectrum matrix metalloproteinase inhibitor, whereas stiffening of the matrix by introducing transglutaminase crosslinking, only induced slight changes in both protrusion size and cell velocity, suggesting that the ability of cells to create a path through the matrix is more critical than the matrix mechanical properties themselves. To confirm this, we developed a cell migration computational model in 3D including both the mechanical and chemical properties of the ECM as well as the protrusion mechanics, obtaining good agreement with experimental results.

中文翻译:

基质降解调节成骨细胞突出动态和个体迁移。

突起是细胞用来探测和探索周围环境以及与其他细胞通信的结构之一。特别是,与其他类型的细胞相比,嵌入3D矩阵中的成骨细胞往往会产生大量突起。在这项工作中,我们研究了细胞外基质(ECM)的机械化学性质在这些突起的动力学上的作用,即对发散结构的大小和数量的调节。此外,我们还确定了突起的动力学如何导致成骨细胞的3D运动。当通过人工广谱基质金属蛋白酶抑制剂阻止金属蛋白酶引起的降解活性时,在突起大小和细胞速度上发现了显着差异。而通过引入转谷氨酰胺酶交联使基质变硬,只会引起突起大小和细胞速度的轻微变化,这表明细胞形成穿过基质的路径的能力比基质本身的机械性能更为关键。为了证实这一点,我们开发了3D细胞迁移计算模型,其中包括ECM的机械和化学特性以及突出力学,并与实验结果取得了很好的一致性。
更新日期:2020-01-10
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