Damji A, Weston L, Brunette D M
Department of Oral Biology, Faculty of Dentistry, The University of British Columbia, Vancouver, Canada.
Exp Cell Res. 1996 Oct 10;228(1):114-24. doi: 10.1006/excr.1996.0306.
Many aspects of cell social behavior, including aspects of tumor invasiveness, embryonic development, and wound healing, can be explained by the principle of contact inhibition (CI) of cell movement. CI refers to the tendency of fibroblasts cultured on a plane substratum to cease movement on contacting other fibroblasts. A problem in studying collisions between cells on a flat substratum is that it is difficult to control the specific regions of the cell that come in contact. In this study we used grooved micromachined titanium substrata to produce collisions between the following cell combinations: fibroblast/fibroblast, fibroblast/epithelium, and epithelium/epithelium. The cells were oriented by the substratum so that the leading lamellae of the cells confronted each other. Cell behaviors before and after contact were observed and recorded using time-lapse cinemicrography employing Nomarski reflected light differential interference microscopy. Electron-microscopy sections were prepared from areas where cell interactions occurred. Fibroblasts (F) moved significantly faster and more persistently on grooved than on smooth surfaces, but the speed of epithelial (E)-cell locomotion was not significantly altered. The grooves, however, guided the direction of locomotion for both cell types. When cultured on grooved surfaces in such a manner that the F and E cells collided head-on, the F, but not the E cells, frequently demonstrated contact inhibition of movement. However, after such collisions, significantly more F continued to invade the E sheet than were observed after F-E collisions on smooth surfaces. After F-F collisions on grooved surfaces, most cells moved to the sides of the grooves and continued in their original directions, while on smooth surfaces they moved off in various different directions. A possible explanation of these observations is that a grooved surface produces and maintains F polarity so that the direction of locomotion is less readily altered by cell-cell interactions.
细胞社会行为的许多方面，包括肿瘤侵袭、胚胎发育和伤口愈合等方面，都可以用细胞运动的接触抑制（CI）原理来解释。CI是指在平面基质上培养的成纤维细胞在与其他成纤维细胞接触时停止运动的倾向。在研究平坦基质上细胞间碰撞时存在一个问题，即难以控制细胞接触的特定区域。在本研究中，我们使用带凹槽的微加工钛基质来促成以下细胞组合之间的碰撞：成纤维细胞/成纤维细胞、成纤维细胞/上皮细胞和上皮细胞/上皮细胞。细胞被基质定向，使得细胞的前缘彼此相对。使用诺马斯基反射光微分干涉显微镜的延时电影显微镜观察并记录接触前后的细胞行为。从细胞相互作用发生的区域制备电子显微镜切片。成纤维细胞（F）在带凹槽的表面上比在光滑表面上移动得更快且更持久，但上皮细胞（E）的运动速度没有显著改变。然而，凹槽引导了两种细胞类型的运动方向。当以F细胞和E细胞正面碰撞的方式在带凹槽的表面上培养时，F细胞而非E细胞经常表现出运动接触抑制。然而，在这种碰撞后，继续侵入E层的F细胞比在光滑表面上F-E碰撞后观察到的要多得多。在带凹槽的表面上F-F碰撞后，大多数细胞移向凹槽的侧面并继续沿其原始方向移动，而在光滑表面上它们则向不同方向散开。对这些观察结果的一种可能解释是，带凹槽的表面产生并维持F细胞的极性，使得运动方向不太容易因细胞间相互作用而改变。
