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聚合物底物组成的微小变化通过最佳配体调节在细胞黏附和运动性方面产生放大的差异。

Minute changes in composition of polymer substrates produce amplified differences in cell adhesion and motility via optimal ligand conditioning.

作者信息

Bae Yong Ho, Johnson Patrick A, Florek Charles A, Kohn Joachim, Moghe Prabhas V

机构信息

Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA.

出版信息

Acta Biomater. 2006 Sep;2(5):473-82. doi: 10.1016/j.actbio.2006.04.001. Epub 2006 Jun 21.

DOI:10.1016/j.actbio.2006.04.001
PMID:16793356
Abstract

We explored the interplay between substratum chemistry of polymeric materials and surface-adsorbed ligand concentration (human plasma fibronectin) in the control of cell adhesion and cell motility. We found that small changes in the chemical composition of a polymeric substratum had different effects on cellular motility--depending on the concentration of preadsorbed fibronectin. We used two tyrosine-derived polyarylates, poly(DTD diglycolate) and poly(DTD glutarate), as substrata for the seeding of NIH-3T3 fibroblasts. The only compositional difference between the two test polymers was that one single oxygen atom in the polymer backbone of poly(DTD diglycolate) had been substituted by a methylene group in the backbone of poly(DTD glutarate), The two polymers had closely matched hydrophobicity and physical properties. Flat, spin-coated surfaces of these polymers were pretreated with different concentrations of human plasma fibronectin (0-20 microg/ml). After seeding with NIH-3T3 fibroblasts, we examined the adhesion and motility behavior of these cells. We found that NIH-3T3 fibroblasts migrated significantly faster on poly(DTD diglycolate), but only when the polymer surfaces were pretreated with intermediate concentrations of fibronectin. Only at these intermediate levels of ligand conditioning, did the presence of an extra oxygen atom in the backbone of poly(DTD diglycolate) relative to poly(DTD glutarate) (i) alter the overall organization/concentration of the fibronectin; (ii) weaken cell attachment strength and inhibited excessive cell spreading; and (iii) promote cell motility kinetics. These findings indicate that the biological effect of minute changes in substratum chemistry is critically dependent on the level of surface-adsorbed cell-binding ligands.

摘要

我们探讨了聚合材料的基质化学与表面吸附配体浓度(人血浆纤连蛋白)在控制细胞黏附和细胞运动方面的相互作用。我们发现,聚合基质化学成分的微小变化对细胞运动有不同影响——这取决于预吸附纤连蛋白的浓度。我们使用两种酪氨酸衍生的聚芳酯,聚(DTD二乙醇酸酯)和聚(DTD戊二酸酯),作为接种NIH-3T3成纤维细胞的基质。两种测试聚合物之间唯一的成分差异是,聚(DTD二乙醇酸酯)聚合物主链中的一个氧原子被聚(DTD戊二酸酯)主链中的一个亚甲基取代,这两种聚合物的疏水性和物理性质紧密匹配。这些聚合物的平坦旋涂表面用不同浓度的人血浆纤连蛋白(0-20微克/毫升)进行预处理。在用NIH-3T3成纤维细胞接种后,我们检查了这些细胞的黏附和运动行为。我们发现,NIH-3T3成纤维细胞在聚(DTD二乙醇酸酯)上迁移得明显更快,但前提是聚合物表面用中等浓度的纤连蛋白进行预处理。只有在这些中等水平的配体调节下,相对于聚(DTD戊二酸酯),聚(DTD二乙醇酸酯)主链中额外氧原子的存在才会(i)改变纤连蛋白的整体组织/浓度;(ii)削弱细胞附着强度并抑制过度的细胞铺展;(iii)促进细胞运动动力学。这些发现表明,基质化学微小变化的生物学效应严重依赖于表面吸附的细胞结合配体的水平。

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