Laboratório de Biomineralização, Centro de Ciênça da Saúde, Instituto De Ciências Biomédicas, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
Université de Haute-Alsace, CNRS, IS2MUMR 7361, 68100, Mulhouse, France.
Sci Rep. 2020 Sep 8;10(1):14784. doi: 10.1038/s41598-020-70907-0.
How biophysical cues can control tissue morphogenesis is a central question in biology and for the development of efficient tissue engineering strategies. Recent data suggest that specific topographies such as grooves and ridges can trigger anisotropic tissue growth. However, the specific contribution of biologically relevant topographical features such as cell-scale curvature is still unclear. Here we engineer a series of grooves and ridges model topographies exhibiting specific curvature at the ridge/groove junctions and monitored the growth of epithelial colonies on these surfaces. We observe a striking proportionality between the maximum convex curvature of the ridges and the elongation of the epithelium. This is accompanied by the anisotropic distribution of F-actin and nuclei with partial exclusion of both in convex regions as well as the curvature-dependent reorientation of pluricellular protrusions and mitotic spindles. This demonstrates that curvature itself is sufficient to trigger and modulate the oriented growth of epithelia through the formation of convex "topographical barriers" and establishes curvature as a powerful tuning parameter for tissue engineering and biomimetic biomaterial design.
生物物理线索如何控制组织形态发生是生物学中的一个核心问题,也是开发高效组织工程策略的关键。最近的数据表明,特定的形貌,如沟槽和脊,可引发各向异性的组织生长。然而,细胞尺度曲率等生物相关形貌特征的具体贡献仍不清楚。在这里,我们设计了一系列具有特定脊/槽交界处曲率的沟槽和脊模型形貌,并监测了上皮细胞集落在这些表面上的生长情况。我们观察到,脊的最大凸曲率与上皮细胞的伸长之间存在显著的比例关系。这伴随着 F-actin 和核的各向异性分布,两者在凸区都被排除在外,并且多细胞突起和有丝分裂纺锤体的曲率依赖性重定向。这表明曲率本身足以通过形成凸形“地形障碍”来触发和调节上皮细胞的定向生长,并确立曲率作为组织工程和仿生生物材料设计的强大调谐参数。