Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Biomaterials. 2013 Nov;34(33):8097-104. doi: 10.1016/j.biomaterials.2013.07.047. Epub 2013 Jul 27.
Cellular organization, migration and proliferation in three-dimensions play a critical role in numerous physiological and pathological processes. Nano- and micro-fabrication approaches have demonstrated that nano- and micro-scale topographies of the cellular microenvironment directly impact organization, migration and proliferation. In this study, we investigated these dynamics of two cell types (NIH3T3 fibroblast and MDCK epithelial cells) in response to microscale grooves whose dimensions exceed typical cell sizes. Our results demonstrate that fibroblasts display a clear preference for proliferating along groove ridges whereas epithelial cells preferentially proliferate in the grooves. Importantly, these cell-type dependent behaviours were also maintained when in co-culture. We show that it is possible to spatially separate a mixed suspension of two cell types by allowing them to migrate and proliferate on a substrate with engineered microtopographies. This ability may have important implications for investigating the mechanisms that facilitate cellular topographic sensing. Moreover, our results may provide insights towards the controlled development of complex three-dimensional multi-cellular constructs.
细胞的三维组织、迁移和增殖在许多生理和病理过程中起着关键作用。纳微制造方法已经证明，细胞微环境的纳米和微尺度形貌直接影响细胞的组织、迁移和增殖。在这项研究中，我们研究了两种细胞类型（NIH3T3 成纤维细胞和 MDCK 上皮细胞）对微尺度沟槽的动力学响应，这些沟槽的尺寸超过了典型的细胞尺寸。我们的结果表明，成纤维细胞明显倾向于沿着沟槽脊增殖，而上皮细胞则优先在沟槽中增殖。重要的是，当两种细胞共培养时，这种细胞类型依赖性的行为仍然存在。我们表明，通过允许两种细胞类型在具有工程微形貌的基底上迁移和增殖，有可能将两种细胞的混合悬浮液在空间上分离。这种能力对于研究促进细胞形貌感知的机制可能具有重要意义。此外，我们的结果可能为控制复杂三维多细胞结构的发展提供了思路。
