Murata Hironobu, Koepsel Richard R, Matyjaszewski Krzysztof, Russell Alan J
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Biomaterials. 2007 Nov;28(32):4870-9. doi: 10.1016/j.biomaterials.2007.06.012. Epub 2007 Aug 15.
Rational controlled synthesis of poly(quaternary ammonium) compounds has been used to prepare antimicrobial polymer brushes on inorganic surfaces. The systematic variation of several structural parameters of the polymeric brushes allowed us to elicit the minimum surface requirements and a probable mechanism of action for Escherichia coli cell kill. Polymeric brushes were prepared by surface-initiated atom transfer radical polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), a method that allows the molecular weight of the polymer chains to be precisely controlled as they grow from the target surface. The tertiary amino groups of the polyDMAEMA were then quaternized with alkyl bromides to provide a surface with antimicrobial activity. Dry layer thickness of the polymer brushes was controlled by polymerization time and/or initiator density on the surface. This tunability of surface structure allows the antimicrobial polymer brushes to be tailored rationally. A combinatorial screening tool was developed to elucidate the role of chain length and chain density on cell kill in a single experiment. The results indicate that surface charge density, is a critical element in designing a surface for maximum kill efficiency. The most biocidal surfaces had charge densities of greater than 1-5 x 10(15) accessible quaternary amine units/cm(2). The relevance of this finding to the mechanism of action is discussed.
聚(季铵)化合物的合理可控合成已被用于在无机表面制备抗菌聚合物刷。聚合物刷的几个结构参数的系统变化使我们能够确定大肠杆菌细胞杀伤的最低表面要求和可能的作用机制。通过甲基丙烯酸2-(二甲氨基)乙酯(DMAEMA)的表面引发原子转移自由基聚合制备聚合物刷,这种方法能够在聚合物链从目标表面生长时精确控制其分子量。然后用烷基溴将聚DMAEMA的叔氨基季铵化,以提供具有抗菌活性的表面。聚合物刷的干层厚度通过聚合时间和/或表面引发剂密度来控制。表面结构的这种可调性使得抗菌聚合物刷能够被合理定制。开发了一种组合筛选工具,以在单个实验中阐明链长和链密度对细胞杀伤的作用。结果表明,表面电荷密度是设计具有最大杀伤效率表面的关键因素。最具杀菌性的表面电荷密度大于1 - 5×10¹⁵个可及季铵单元/cm²。讨论了这一发现与作用机制的相关性。