Nanofiber curvature with Rho GTPase activity increases mouse embryonic fibroblast random migration velocity.
Nanofiber curvature with Rho GTPase activity increases mouse embryonic fibroblast random migration velocity.
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DOI：
10.1093/intbio/zyab022
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发表时间：
2021-12
期刊：
影响因子：
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通讯作者：
D. T. Bowers;Justin L. Brown
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文献类型：
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作者：
D. T. Bowers;Justin L. Brown
机械转导源于材料形状（如曲率）中编码的信息。它诱导小GTPase信号的激活，影响细胞表型，包括分化。我们进行了一系列初步实验，以验证曲率（1/半径）也会由于信号通路串扰而影响细胞运动的假设。采用静电纺丝法制备了曲率为41 ~ 1 μm-1的高分子量聚甲基丙烯酸甲酯直线型纳米纤维，并在钝化玻璃衬底上收集。纤维曲率增加小鼠间充质干细胞长径比（P < 0.02），减少细胞面积（P < 0.01）。尽管对某些运动模式（如极性和持久性）几乎没有影响，但我们发现，与平坦表面相比，选定的纤维曲率可以使归一化随机成纤维小鼠胚胎细胞（MEF）的迁移速度提高近2.5倍（P < 0.001）。速度曲线的最大值出现在2.5 μm-1附近，并随附着时间（0 ~ 20 h）的变化而变化。在纤维曲率的中间范围内，rho激酶抑制剂（Y27632）或cdc42抑制剂（ML141）与曲率的相对关系相似，尽管在大多数曲率上有所降低（P < 0.05）。然而，低于临界曲率阈值，mef可能无法区分浅曲率和平面，同时仍然受到接触制导的影响。本文的初步数据表明，大的低曲率纤维被解释为类似于非曲面的方式。因此，曲率是一个生物材料结构设计参数，当需要特定的生物反应时，应该考虑它。整合、创新和洞见对无法再生的受损或病变组织的替换正在改变现代医学。然而，我们能够合理设计材料来影响细胞结果的程度仍然很低。了解材料刚度和直径对干细胞分化的影响，我们研究了纤维支架上的细胞迁移和信号传导。通过研究不同数量级（50-2000纳米）的直径，我们确定了最大速度约800纳米。此外，结果表明，大纤维可能不会被单个细胞解释为曲面。这项工作提出了洞察工程组织结构的设计。
Mechanotransduction arises from information encoded in the shape of materials such as curvature. It induces activation of small GTPase signaling affecting cell phenotypes including differentiation. We carried out a set of preliminary experiments to test the hypothesis that curvature (1/radius) would also affect cell motility due to signal pathway crosstalk. High molecular weight poly (methyl methacrylate) straight nanofibers were electrospun with curvature ranging from 41 to 1 μm-1 and collected on a passivated glass substrate. The fiber curvature increased mouse mesenchymal stem cell aspect ratio (P < 0.02) and decreased cell area (P < 0.01). Despite little effect on some motility patterns such as polarity and persistence, we found selected fiber curvatures can increase normalized random fibroblastic mouse embryonic cell (MEF) migration velocity close to 2.5 times compared with a flat surface (P < 0.001). A maximum in the velocity curve occurred near 2.5 μm-1 and may vary with the time since initiation of attachment to the surface (range of 0-20 h). In the middle range of fiber curvatures, the relative relationship to curvature was similar regardless of treatment with Rho-kinase inhibitor (Y27632) or cdc42 inhibitor (ML141), although it was decreased on most curvatures (P < 0.05). However, below a critical curvature threshold MEFs may not be able to distinguish shallow curvature from a flat surface, while still being affected by contact guidance. The preliminary data in this manuscript suggested the large low curvature fibers were interpreted in a manner similar to a non-curved surface. Thus, curvature is a biomaterial construct design parameter that should be considered when specific biological responses are desired. Statement of integration, innovation, and insight Replacement of damaged or diseased tissues that cannot otherwise regenerate is transforming modern medicine. However, the extent to which we can rationally design materials to affect cellular outcomes remains low. Knowing the effect of material stiffness and diameter on stem cell differentiation, we investigated cell migration and signaling on fibrous scaffolds. By investigating diameters across orders of magnitude (50-2000 nm), we identified a velocity maximum of ~800 nm. Furthermore, the results suggest large fibers may not be interpreted by single cells as a curved surface. This work presents insight into the design of constructs for engineering tissues.