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Mechanistic Insights and Rational Design of a Versatile Surface with Cells/Bacteria Recognition Capability via Orientated Fusion Peptides

机译:通过定向融合肽具有细胞/细菌识别能力的多功能表面的机械原理和合理设计

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摘要

Hospital‐acquired infection causes many deaths worldwide and calls for the urgent need for antibacterial biomaterials used in clinic that can selectively kill harmful bacteria. The present study rationally designs fusion peptides capable of undergoing 2D self‐assembly on the poly(methyl methacrylate) surface to form a smart surface, which can maintain a desirable orientation via electrostatic interactions. The in vitro assay shows that the smart surface can recognize bacteria to exert antibacterial activity and is nontoxic toward mouse bone mesenchymal stem cells. Excitingly, the smart surface can distinguish different bacterial strains. This selective feature, from being broad‐spectrum to being highly selective against S. aureus, can be altered by varying the number of amino acids in the recognition sequences. By all‐atom molecular dynamics simulations, it is also found that the recognition sequence in the peptide is critical for the selectivity toward specific bacterial strains, in which a less accessible surface area for the bacteria in the antimicrobial peptide sequence is responsible for such selectivity. Finally, the smart surface can inhibit S. aureus infection in vivo with much more rapid tissue‐healing compared to the control.
机译:医院获得性感染导致全世界许多人死亡,因此迫切需要用于临床的可选择性杀死有害细菌的抗菌生物材料。本研究合理地设计了能够在聚甲基丙烯酸甲酯表面上进行二维自组装以形成智能表面的融合肽,该表面可以通过静电相互作用保持理想的取向。体外测定表明,智能表面可以识别细菌发挥抗菌活性,并且对小鼠骨骼间充质干细胞无毒。令人兴奋的是,智能表面可以区分不同的细菌菌株。从广谱到对金黄色葡萄球菌具有高度选择性的这种选择性特征,可以通过改变识别序列中的氨基酸数目来改变。通过全原子分子动力学模拟,还发现,肽中的识别序列对于针对特定细菌菌株的选择性至关重要,其中抗菌肽序列中细菌接触不到的表面积是造成这种选择性的原因。最后,与对照相比,智能表面可以在体内抑制金黄色葡萄球菌感染,并且组织愈合快得多。

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