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Functional Fibronectin Adsorption on Aptamer-Doped Chitosan Modulates Cell Morphology by Integrin-Mediated Pathway

机译:功能性纤连蛋白在适体掺杂壳聚糖上的吸附通过整合素介导的途径调节细胞形态。

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摘要

A decisive step in cell-biomaterial interaction is represented by the adsorption of proteins at the interface, whose fine control may be useful to trigger proper cell response. To this purpose, we can selectively control protein adsorption on biomaterials by means of aptamers. Aptamers selected to recognize fibronectin dramatically enhance chitosan ability to promote cell proliferation and adhesion, but the underlying biological mechanism remains unknown. We supposed that aptamers contributed to ameliorate the adsorption of fibronectin in an advantageous geometrical conformation for cells, thus regulating their morphology by the proper activation of the integrin-mediated pathway. We investigated this possibility by culturing epithelial cells on chitosan enriched with increasing doses of aptamers in the presence or in the absence of cytoskeleton pharmacological inhibitors. Our results showed that aptamers control cell morphology in a dose dependent manner (p < 0.0001). Simultaneously, when the inhibition of actin polymerization was induced, the control of cell morphology was attenuated (p < 0.0001), while no differences were detected when cells contractility was challenged (p > 0.05). Altogether, our data provide evidence that aptamers contribute to control fibronectin adsorption on biomaterials by preserving its conformation and thus function. Furthermore, our work provides a new insight into a new way to accurately tailor material surface bioactivity.
机译:细胞与生物材料相互作用的决定性步骤是界面处蛋白质的吸附,其精细控制可用于触发适当的细胞反应。为此,我们可以通过适体选择性地控制蛋白质在生物材料上的吸附。选择识别纤连蛋白的适体极大地增强了壳聚糖促进细胞增殖和粘附的能力,但是其潜在的生物学机制仍然未知。我们认为适体有助于改善纤连蛋白在细胞的有利几何构型中的吸附,从而通过整联蛋白介导的途径的适当活化来调节其形态。我们通过在存在或不存在细胞骨架药理抑制剂的情况下,在富含剂量增加的适体的壳聚糖上培养上皮细胞来研究这种可能性。我们的结果表明,适体以剂量依赖性方式控制细胞形态(p <0.0001)。同时,当诱导肌动蛋白聚合的抑制作用时,细胞形态的控制减弱(p <0.0001),而当细胞收缩性受到挑战时则没有发现差异(p> 0.05)。总而言之,我们的数据提供了证据,表明适体通过保留其构象并因此发挥功能来控制纤连蛋白在生物材料上的吸附。此外,我们的工作为准确定制材料表面生物活性的新方法提供了新见解。

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