Antimicrobial peptides (AMPs), as a key component of the immune defense systems of organisms, are a promising solution to the serious threat of drug-resistant bacteria to public health. As one of the most representative and extensively studied AMPs, melittin has exceptional broad-spectrum activities against microorganisms, including both Gram-positive and Gram-negative bacteria. Unfortunately, the action mechanism of melittin with bacterial membranes, especially the underlying physics of peptide-induced membrane poration behaviors, is still poorly understood, which hampers efforts to develop melittin-based drugs or agents for clinical applications. In this mini-review, we focus on recent advances with respect to the membrane insertion behavior of melittin mostly from a computational aspect. Membrane insertion is a prerequisite and key step for forming transmembrane pores and bacterial killing by melittin, whose occurrence is based on overcoming a high free-energy barrier during the transition of melittin molecules from a membrane surface-binding state to a transmembrane-inserting state. Here, intriguing simulation results on such transition are highlighted from both kinetic and thermodynamic aspects. The conformational changes and inter-peptide cooperation of melittin molecules, as well as melittin-induced disturbances to membrane structure, such as deformation and lipid extraction, are regarded as key factors influencing the insertion of peptides into membranes. The associated intermediate states in peptide conformations, lipid arrangements, membrane structure, and mechanical properties during this process are specifically discussed. Finally, potential strategies for enhancing the poration ability and improving the antimicrobial performance of AMPs are included as well.

The fundamental differences in phospholipids between bacterial and mammalian cell membranes present remarkable opportunities for antimicrobial design. However, it is challenging to distinguish bacterial anionic phospholipid phosphatidylglycerol (PG) from mammalian anionic phosphatidylserine (PS) with the same net charge. Here, we report a class of radially amphiphilic α helix antimicrobial peptides (RAPs) that can selectively discriminate PG from PS, relying on the helix structure. The representative RAP, L ₁₀ -MMBen, can direct the rearrangement of PG vesicles into a lamellar structure with its helix axis parallel to the PG membrane surface. The helical structure imparts both the thermodynamic and kinetic advantages of L ₁₀ -MMBen/PG assembly, and the hiding of hydrophobic regions in RAPs is crucial for PG recognition. L ₁₀ -MMBen exhibits high selectivity against bacteria depending on PG recognition, showing low in vivo toxicity and significant treatment efficacy in mice infection models. Our study introduces a helicity-direct bacterial phospholipid recognition paradigm for designing highly selective antimicrobial peptides.

The presence of unpaired electrons (radicals) due to structural defects is believed to contribute to the catalytic reactivity of carbon materials. Graphite oxide and graphene oxide (GO) consist of significant structural defects and hence are considered more reactive than graphite and graphene. However, the relationship between their radical content/reactivity and their physical and chemical structures remains unknown, which limits the fabrication of high efficiency carbon-based catalysts. In this work, we progressively oxidize graphite to achieve graphite oxide and GO with different levels of oxidation and different sizes. It is observed that a maximal radical content can be achieved on graphite oxide with a C/O ratio of ca. 3.0 and a thickness of around 50 nm. Such a graphite oxide contains about 45% of π bonds and 38% of oxygenated bonds, respectively. Thinner or thicker sheets have lower radical contents due to over or insufficient oxidation, respectively. Single GO sheets with high radical contents can only be produced through a combination of oxidation and reduction. The catalytic activity of the graphite/graphene oxide for phenol degradation was found to be linearly correlated to their radical contents. The observations are significant for the advancement of carbon-based metal-free catalysis.