Chemical Modification of Reactive Multilayered Films Fabricated from Poly(2-alkenyl azlactone)s: Design of Surfaces that Prevent or Promote Mammalian Cell Adhesion and Bacterial Biofilm Growth
Chemical Modification of Reactive Multilayered Films Fabricated from Poly(2-alkenyl azlactone)s: Design of Surfaces that Prevent or Promote Mammalian Cell Adhesion and Bacterial Biofilm Growth
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DOI：
10.1021/bm9001552
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发表时间：
2009-06-01
影响因子：
6.2
通讯作者：
Lynn, David M.
中科院分区：
文献类型：
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作者：
Buck, Maren E.;Breitbach, Anthony S.;Lynn, David M.
我们报告了一种设计反应性聚合物膜的方法，该反应性聚合物膜可以在制造后被官能化以防止或促进细胞的附着和生长。我们的方法是基于使用合成的聚胺和含有反应性吖内酯官能团的聚合物的共价交联薄膜的反应性逐层组装。我们的研究结果表明：（i）这些膜中的残余吖内酯官能团可以被利用来形成类似于那些促进或阻止细胞和蛋白质粘附的化学基序，当组装成在金涂覆表面上的自组装单层时，以及（ii）这些基序的固定化显著改变了细胞与这些聚合物膜表面的行为和相互作用。我们证明了用疏水分子癸胺处理的膜支持体外哺乳动物细胞的附着和生长。相反，用亲水性碳水化合物D-葡糖胺处理的膜几乎完全阻止细胞粘附和生长。额外的实验结果表明，这些细胞行为的巨大差异可以理解，至少部分地，在这两种不同的化学基序的能力的差异，以促进或防止蛋白质吸附到膜包被的表面。我们进一步证明，这种方法可用于图案化这些反应膜的区域，这些反应膜在含血清的细胞培养基存在下抵抗哺乳动物细胞的初始附着和随后的入侵至少一个月。最后，我们报告说，电影，防止哺乳动物细胞的粘附和生长，也防止细菌生物膜的初始形成时，在临床相关的病原体铜绿假单胞菌的存在下孵育。这些研究的结果，总的来说，建议的基础上的一般方法的制造和功能化的薄膜，防止，促进，或图案细胞生长或形成的生物膜的表面上的利益的背景下，基础生物学研究和广泛的其他实际应用。
We report an approach to the design of reactive polymer films that can be functionalized post-fabrication to either prevent or promote the attachment and growth of cells. Our approach is based on the reactive layer-by-layer assembly of covalently crosslinked thin films using a synthetic polyamine and a polymer containing reactive azlactone functionality. Our results demonstrate (i) that the residual azlactone functionality in these films can be exploited to immobilize amine-functionalized chemical motifs similar to those that promote or prevent cell and protein adhesion when assembled as self-assembled monolayers on gold-coated surfaces and (ii) that the immobilization of these motifs changes significantly the behaviors and interactions of cells with the surfaces of these polymer films. We demonstrate that films treated with the hydrophobic molecule decylamine support the attachment and growth of mammalian cells in vitro. In contrast, films treated with the hydrophilic carbohydrate D-glucamine prevent cell adhesion and growth almost completely. The results of additional experiments suggest that these large differences in cell behavior can be understood, at least in part, in terms of differences in the abilities of these two different chemical motifs to promote or prevent the adsorption of protein onto film-coated surfaces. We demonstrate further that this approach can be used to pattern regions of these reactive films that resist the initial attachment and subsequent invasion of mammalian cells for periods of at least one month in the presence of serum-containing cell culture media. Finally, we report that films that prevent the adhesion and growth of mammalian cells also prevent the initial formation of bacterial biofilms when incubated in the presence of the clinically relevant pathogen Pseudomonas aeruginosa. The results of these studies, collectively, suggest the basis of general approaches to the fabrication and functionalization of thin films that prevent, promote, or pattern cell growth or the formation of biofilms on surfaces of interest in the contexts of both fundamental biological studies and a broad range of other practical applications.