Revealing Molecular-Level Interaction between a Polymeric Drug and Model Membrane Via Sum Frequency Generation and Microfluidics

Body fluids flow all over the body and affect the biological processes at biointerfaces. To simulate such a case, sum frequency generation (SFG) vibrational spectroscopy and a self-designed microfluidic chip were combined together to investigate the interaction between a pH-responsive polymeric drug, poly(alpha-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 affecting 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 pH 6.6, the interaction between PPAAc and the model cell membrane was strongest; with flowing, at pH 5.8, the interaction was strongest. Flowing was proven to substantially affect the interaction between PPAAc and the model cell membranes, suggesting that the fluid environment was of key significance for biointerfaces. 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 collecting the normal static SFG spectra.