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

Abstract 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.