Surface-induced changes in protein adsorption and implications for cellular phenotypic responses to surface interaction
Surface-induced changes in protein adsorption and implications for cellular phenotypic responses to surface interaction
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DOI：
10.1016/j.biomaterials.2006.01.019
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发表时间：
2006-06-01
期刊：
影响因子：
14
通讯作者：
Gallagher, WM
中科院分区：
文献类型：
--
作者：
Allen, LT;Tosetto, M;Gallagher, WM
了解决定细胞表型反应的外部因素是生物材料领域的主要兴趣。目前，材料表面特性、蛋白质吸附和细胞表型反应都被认为是相互关联的，并最终决定材料的生物相容性。这些不同但相关的现象之间关系的确切性质仍有待阐明。通过使用一系列基于 N-异丙基丙烯酰胺的热响应性共聚物薄膜，我们旨在阐明表面疏水性、蛋白质吸附和随后的细胞反应之间的关系。尽管通过改变组成单体的比例介导了共聚物疏水性的变化，但差异细胞反应仅在存在血清的情况下才明显。共聚物膜显示出表面吸附的蛋白质量的变化，各个血清蛋白（白蛋白和纤连蛋白）显示出对比的吸附特性。蛋白质吸附的变化对应于细胞粘附、细胞骨架组织和细胞形态的变化，以及细胞运动和细胞内信号传导事件的变化。对粘附斑激酶 (FAK) 和细胞外信号调节激酶 (ERK 1/2)（粘附和生长因子相关信号事件的重要介质）的检查表明，与在组织培养聚苯乙烯（TCP；用作对照表面）上培养的细胞相比，在共聚物上生长的细胞中这些信号蛋白的磷酸化相对减少。我们还将 TCP 和共聚物薄膜上生长的细胞的表面介导的表型改变与基因表达的特定变化联系起来。这些结果表明，细胞对与我们的系列共聚物膜相互作用的反应是由表面吸附的蛋白质层决定的，而表面吸附的蛋白质层又是由随着共聚单体的比例改变而改变的表面化学性质决定的。 (c) 2006 Elsevier Ltd. 保留所有权利。
Understanding external factors that determine cellular phenotypic responses is of key interest in the field of biomaterials. Currently, material surface characteristics, protein adsorption and cellular phenotypic responses are all considered to be interrelated and ultimately determine the biocompatibility of materials. The exact nature of the relationship between these distinct, yet related, phenomena still remains to be elucidated. Through the use of a series of thermoresponsive N-isopropylacrylamide-based co-polymer films, we aimed to shed light on the relationship between surface hydrophobicity, protein adsorption and subsequent cellular response. Despite changes in co-polymer hydrophobicity mediated by altered ratios of constituent monomers, differential cellular response was only apparent in the presence of serum. Co-polymer films displayed alterations with respect to the amount of protein adsorbed on the surface, with individual serum proteins (albumin and fibronectin) displaying contrasting adsorption characteristics. Changes in protein adsorption corresponded to changes in cell adhesion, cytoskeletal organisation and cell morphology, as well as to changes in cell movement and intracellular signalling events. Examination of focal adhesion kinase (FAK), and extracellular signal-regulated kinase (ERK 1/2), important mediators of adhesion and growth factor-related signalling events, revealed a comparative reduction in phosphorylation of these signalling proteins in cells grown on co-polymers in comparison to those cultured on tissue culture polystyrene (TCP; used as a control surface). We also associated surface-mediated phenotypic alterations of cells grown on TCP and co-polymer films with particular changes in gene expression. These results indicate that cellular response to interaction with our series of co-polymer films is determined by the surface-adsorbed protein layer, which in turn is determined by the changing surface chemistry as the ratio of the co-monomers is altered. (c) 2006 Elsevier Ltd. All rights reserved.