Department of Bioengineering, University of California, Berkeley, California 94720, USA.
Lab Chip. 2012 Jul 7;12(13):2391-402. doi: 10.1039/c2lc40084g. Epub 2012 Apr 25.
Directed cell migration is critical to a variety of biological and physiological processes. Although simple topographical patterns such as parallel grooves and three-dimensional post arrays have been studied to guide cell migration, the effect of the dimensions and shape of micropatterns, which respectively represent the amount and gradient of physical spatial cues, on cell migration has not yet been fully explored. This motivates a quantitative characterization of cell migration in response to micropatterns having different widths and divergence angles. The changes in the migratory (and even locational) behavior of adherent cells, when the cells are exposed to physical spatial cues imposed by the micropatterns, are explored here using a microfabricated biological platform, nicknamed the "Rome platform". The Rome platform, made of a biocompatible, ultraviolet (UV) curable polymer (ORMOCOMP), consists of 3 μm thick micropatterns with different widths of 3 to 75 μm and different divergence angles of 0.5 to 5.0°. The migration paths through which NIH 3T3 fibroblasts move on the micropatterns are analyzed with a persistent random walk model, thus quantifying the effect of the divergence angle of micropatterns on cell migratory characteristics such as cell migration speed, directional persistence time, and random motility coefficient. The effect of the width of micropatterns on cell migratory characteristics is also extensively investigated. Cell migration direction is manipulated by creating the gradient of physical spatial cues (that is, divergence angle of micropatterns), while cell migration speed is controlled by modulating the amount of them (namely, width of micropatterns). In short, the amount and gradient of physical spatial cues imposed by changing the width and divergence angle of micropatterns make it possible to control the rate and direction of cell migration in a passive way. These results offer a potential for reducing the healing time of open wounds with a smart wound dressing engraved with micropatterns (or microscaffolds).
定向细胞迁移对于多种生物学和生理学过程至关重要。尽管已经研究了简单的形貌图案，如平行槽和三维柱阵列，以引导细胞迁移，但微图案的尺寸和形状对细胞迁移的影响尚未得到充分探索，微图案分别代表物理空间线索的数量和梯度。这促使我们定量研究细胞对具有不同宽度和发散角的微图案的迁移反应。本文使用一种名为“罗马平台”的微制造生物平台来探索当细胞暴露于微图案施加的物理空间线索时，贴壁细胞的迁移（甚至定位）行为的变化。罗马平台由生物相容性的紫外（UV）可固化聚合物（ORMOCOMP）制成，由宽度为 3 至 75μm、发散角为 0.5 至 5.0°的不同宽度的 3μm 厚微图案组成。通过持久随机游走模型分析 NIH 3T3 成纤维细胞在微图案上的迁移路径，从而量化微图案发散角对细胞迁移速度、定向持久性时间和随机迁移系数等细胞迁移特征的影响。还广泛研究了微图案宽度对细胞迁移特征的影响。通过创建物理空间线索的梯度（即微图案的发散角）来操纵细胞迁移方向，通过调节物理空间线索的数量（即微图案的宽度）来控制细胞迁移速度。简而言之，通过改变微图案的宽度和发散角来施加物理空间线索的数量和梯度，可以被动地控制细胞迁移的速度和方向。这些结果为使用刻有微图案（或微支架）的智能伤口敷料来减少开放性伤口的愈合时间提供了一种可能性。
