Zaman Muhammad H, Matsudaira Paul, Lauffenburger Douglas A
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Ann Biomed Eng. 2007 Jan;35(1):91-100. doi: 10.1007/s10439-006-9205-6. Epub 2006 Nov 2.
Recent studies have shown significant differences in migration mechanisms between two- and three-dimensional environments. While experiments have suggested a strong dependence of in vivo migration on both structure and proteolytic activity, the underlying biophysics of such dependence has not been studied adequately. In addition, the existing models of persistent random walk migration are primarily based on two-dimensional movement and do not account for the effect of proteolysis or matrix inhomogeneity. Using lattice Monte Carlo methods, we present a model to study the role of matrix metallo-proteases (MMPs) on directional persistence and speed. The simulations account for a given cell's ability to deform as well as to digest the matrix as the cell moves in three dimensions. Our results show a bimodal dependence of speed and persistence on matrix pore size and suggest high sensitivity on MMP activity, which is in very good agreement with experimental studies carried out in 3D matrices.
最近的研究表明，二维和三维环境中的迁移机制存在显著差异。虽然实验表明体内迁移强烈依赖于结构和蛋白水解活性，但这种依赖性背后的生物物理学尚未得到充分研究。此外，现有的持续随机游走迁移模型主要基于二维运动，没有考虑蛋白水解或基质不均匀性的影响。我们使用晶格蒙特卡罗方法提出了一个模型，以研究基质金属蛋白酶（MMPs）对方向持续性和速度的作用。模拟考虑了给定细胞在三维空间中移动时的变形能力以及消化基质的能力。我们的结果表明，速度和持续性对基质孔径呈双峰依赖性，并表明对MMP活性高度敏感，这与在三维基质中进行的实验研究非常吻合。
