Revealing Molecular-level Interaction Between A Polymeric Drug And Model Membrane Via Sfg And Microfluidics

Drug-membrane interactions happening at bio-interfaces are one of the most important biological issues in biomedical science and engineering.Among current spectroscopic methods,sum frequency generation(SFG)vibrational spectroscopy,is one of the best choices to investigate the drug-membrane interactions.To simulate flow environment,SFG and a self-designed microfluidic chip were combined together to investigate the interaction between a p H-responsive polymeric drug,poly(α-propylacrylic acid)(PPAAc)and the model cell membranes in different liquid environments.By examining the SFG spectra under the static and flowing conditions,the drug-membrane interaction was revealed comprehensively.The interfacial water layer was screened as the key factor to affect the drug-membrane interaction.The interfacial water layer can prevent the side propyl groups on PPAAc from inserting into the model cell membrane,but would be disrupted by numerous ions in buffer solutions.Without flowing,at p H 6.6,the interaction between PPAAc and the model cell membrane was strongest;with flowing,at p H 5.8,the interaction was strongest.Flowing was proved to substantially affect the interaction between PPAAc and the model cell membranes,suggesting that the fluid environment was of key significance for bio-interfaces.This work demonstrated that,by combining SFG and microfluidics,new information about the molecular-level interaction between macromolecules and the model cell membranes can be acquired,which cannot be obtained by running the normal static SFG experiments.Furthermore,the peptide-membrane interaction was investigated.Aurein 1.2 is a13-amino acid peptide.With increasing concentration of Aurein 1.2,the outer leaflet of the biomembrane was gradually disturbed,while the inner leaflet remained unchanged.It was demonstrated that the phenyl groups on Aurein 1.2 could reflect the peptide’s behavior,such as lying or standing.More kinds of peptides will be employed to illustrate the different models of peptide-biomembrane interactions in the future.