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多孔基质以牺牲纤连蛋白原纤维形成的代价促进内皮细胞迁移。

Porous Substrates Promote Endothelial Migration at the Expense of Fibronectin Fibrillogenesis.

作者信息

Chung Henry H, Casillo Stephanie M, Perry Spencer J, Gaborski Thomas R

机构信息

Department of Biomedical Engineering, Rochester Institute of Technology, 160 Lomb Memorial Drive, Rochester, New York 14623, United States.

出版信息

ACS Biomater Sci Eng. 2018 Jan 8;4(1):222-230. doi: 10.1021/acsbiomaterials.7b00792. Epub 2017 Nov 28.

Abstract

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 two-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.

摘要

多孔基质在细胞研究和组织模拟应用中的使用越来越广泛,因为它们可以分隔不同的细胞类型,同时仍允许重要的生化串扰。在本研究中,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以及相关的细胞外基质(ECM)形成,这可能会严重影响细胞在基质上的覆盖速度和随后的组织形成。我们通过延时显微镜观察发现,在具有0.5μm孔隙的膜上,细胞速度和迁移距离几乎是非多孔膜上观察到的值的两倍,而在具有3.0μm孔隙的膜上的值则介于两者之间。尽管孔隙的存在并未影响细胞的方向性比率和持续时间,但细胞确实基于六边形孔隙图案表现出方向性偏好。纤连蛋白的纤维形成与细胞速度呈现出明显的反比关系,因为在无孔对照上形成的纤维明显长于两种多孔基质上的纤维。我们进一步在单个细胞的基础上证实,纤连蛋白纤维长度与细胞速度之间存在负相关。因此,在为组织模拟应用选择或设计理想的多孔基质时,需要考虑早期细胞覆盖和ECM形成之间观察到的权衡,这可能有助于指导未来的细胞研究。

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