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Porous Substrates Promote Endothelial Migration at the Expense of Fibronectin Fibrillogenesis
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2017-12-11 00:00:00 , DOI: 10.1021/acsbiomaterials.7b00792
Henry H. Chung 1 , Stephanie M. Casillo 1 , Spencer J. Perry 1 , Thomas R. Gaborski 1
Affiliation  

Porous substrates have gained increased usage in cell studies and tissue mimetic applications because they can partition distinct cell types while still allowing important biochemical crosstalk. In the presented work, we investigated how porous substrates with micron and submicron features influence early cell migration and the associated ECM establishment, which can critically affect the rate of cell coverage on the substrate and the ensuing tissue organization. We showed through time-lapse microscopy that cell speed and migratory distance on membranes with 0.5 μm pores were nearly 2-fold of those observed on nonporous membranes, while values on membranes with 3.0 μm pores fell in between. Although the cell directionality ratio and the persistence time was unaffected by the presence of pores, the cells did exhibit directionality preferences based on the hexagonal pore patterning. Fibronectin fibrillogenesis exhibited a distinct inverse relationship to cell speed, as the fibrils formed on the nonporous control were significantly longer than those on both types of porous substrates. We further confirmed on a per cell basis that there is a negative correlation between fibronectin fibril length and cell speed. The observed trade-off between early cell coverage and ECM establishment thus warrants consideration in the selection or the engineering of the ideal porous substrate for tissue mimetic applications and may help guide future cell studies.

中文翻译:

多孔底物以纤连蛋白原纤维形成为代价促进内皮迁移

多孔底物在细胞研究和组织模拟应用中得到了越来越多的使用,因为它们可以划分不同的细胞类型,同时仍然允许重要的生化串扰。在提出的工作中,我们研究了具有微米和亚微米特征的多孔基质如何影响早期细胞迁移和相关的ECM建立,这可以严重影响基质上细胞的覆盖率和随后的组织组织。我们通过延时显微镜显示,具有0.5μm孔的膜上的细胞速度和迁移距离几乎是无孔膜上观察到的2倍,而具有3.0μm孔的膜上的值介于两者之间。尽管细胞方向性比率和持续时间不受孔的存在的影响,这些细胞确实显示出基于六边形孔图案的方向性偏好。纤连蛋白的原纤维形成与细胞速度呈明显的反比关系,因为在无孔对照上形成的原纤维明显长于在两种类型的多孔底物上形成的原纤维。我们进一步证实,在每个细胞的基础上,纤连蛋白原纤维长度与细胞速度之间存在负相关。因此,在早期细胞覆盖和ECM建立之间观察到的折衷值得在组织模拟应用的理想多孔基质的选择或工程设计中加以考虑,并可能有助于指导未来的细胞研究。因为在无孔对照上形成的原纤维明显长于两种类型的多孔基质上的原纤维。我们进一步证实,在每个细胞的基础上,纤连蛋白原纤维长度与细胞速度之间存在负相关。因此,在早期细胞覆盖和ECM建立之间观察到的折衷值得在组织模拟应用的理想多孔基质的选择或工程设计中加以考虑,并可能有助于指导未来的细胞研究。因为在无孔对照上形成的原纤维明显长于两种类型的多孔基质上的原纤维。我们进一步证实,在每个细胞的基础上,纤连蛋白原纤维长度与细胞速度之间存在负相关。因此,在早期细胞覆盖和ECM建立之间观察到的折衷值得在组织模拟应用的理想多孔基质的选择或工程设计中加以考虑,并可能有助于指导未来的细胞研究。
更新日期:2017-12-11
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