Simultaneous characterization of protein-material and cell-protein interactions using dynamic QCM-D analysis on SAM surfaces

Understanding the interactions among materials, proteins and cells is critical for the development of novel biomaterials, and establishing a highly sensitive and quantitative method to standardize these interactions is desired. In this study, quartz crystal microbalance with dissipation (QCM-D) combined with microscopy was utilized to quantitatively monitor the entirety of the cell adhesion processes, starting from the protein adsorption, on various self-assembled monolayer (SAM) surfaces. Although the resulting cell adhesion morphologies were similar on most of the surfaces, the dynamic QCM-D signal patterns were unique on each surface, suggesting different forms of material-protein-cell interactions. The viscoelasticity and the density of the surface-adsorbed fibronectin (FN), as well as the relative exposure of the cell adhesive arginine-glycine-aspartic acid (RGD) motifs, were correlated to the different cell adhesion dynamics and mechanics. Some surfaces exhibited complicated behaviors alluding to the detachment/rearrangement of surface proteins or highly sparse but bioactive proteins that promote a slow adhesion process. This study underscores the potential use of the QCM-D signal pattern as a rule of thumb for delineating different protein-material and cell-protein interactions, and offers a rapid in vitro platform for the dynamic evaluation of protein and cell behaviors on novel biomaterials.