Kirmse Robert, Otto Hannes, Ludwig Thomas
Commun Integr Biol. 2012 Jan 1;5(1):71-3. doi: 10.4161/cib.17342.
Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP-14) is regarded as the prototype of a membrane- tethered protease. It drives fundamental biological processes ranging from embryogenesis to cancer metastasis. The proteolytic cleavage of proteins by MT1-MMP can rapidly alter the biophysical properties of a cell's microenvironment. Cell's must thus be able to sense and react to these alterations and transduce these effectively in biochemical signals and cell responses. Although many cells react as acutely to such physical stimuli as they do to chemical ones, the regulatory effects of these have been less extensively explored. In order to investigate a possible interdependency of proteolytic matrix cleavage by MT1-MMP and the generation and sensing of force by cells, a model system was established which exploits the properties of a matrix array of parallel collagen-I fibers. The resulting an-isotropy of the matrix with high tensile strength along the fibers and high mobility perpendicular to it allows the convenient detection of bundling and cleavage of the collagen fibers, as well as spreading and durotaxis of the cells. In summary, we have demonstrated that cell adhesion, force generation, and force sensing are vital for the regulation of MT1-MMP for efficient cleavage of collagen-I.
膜型-1基质金属蛋白酶（MT1-MMP，MMP-14）被视为膜锚定蛋白酶的原型。它驱动着从胚胎发生到癌症转移等一系列基本生物学过程。MT1-MMP对蛋白质的蛋白水解切割能够迅速改变细胞微环境的生物物理特性。因此，细胞必须能够感知并对这些改变做出反应，并将其有效地转化为生化信号和细胞反应。尽管许多细胞对这种物理刺激的反应与对化学刺激的反应一样敏锐，但对这些刺激的调节作用的探索却较少。为了研究MT1-MMP对蛋白水解性基质切割与细胞产生和感知力之间可能存在的相互依赖性，建立了一个利用平行I型胶原纤维基质阵列特性的模型系统。由此产生的基质各向异性，即沿纤维方向具有高拉伸强度，垂直于纤维方向具有高流动性，便于检测胶原纤维的束集和切割，以及细胞的铺展和趋硬性。总之，我们已经证明细胞黏附、力的产生和力的感知对于MT1-MMP有效切割I型胶原的调节至关重要。
