From pathogen intrusion to immune response, the cell membrane plays an important role in signal transduction. Such signals are important for cellular proliferation and survival. However, measurement of these subtle signals through the lipid membrane scaffold is challenging. We present a chromatic model membrane vesicle system engineered to covalently bind with lysine residues of protein molecules for investigation of cellular interactions and signaling. We discovered that different protein molecules induced differential spectroscopic signals, which is based on the chemical and physical properties of protein interacting at the vesicle surface. The observed chromatic response (CR) for bound protein molecules with higher molecular weight was much larger (∼5-15×) than those for low molecular weight proteins. Through mass spectrometry (MS), we found that only 6 out of 60 (10%) lysine groups present in bovine serum albumin (BSA) were accessible to the membrane of the vesicles. Finally, a "sphere-shell" model representing the protein-vesicle complex was used for evaluating the contribution of van der Waals interactions between proteins and vesicles. Our analysis points to contributions from van der Waals, hydrophobic, and electrostatic interactions toward observed CR signals resulting from molecular interactions at the vesicle membrane surface. Overall, this study provided a convenient, chromatic, semiquantitative method of detecting biomolecules and their interactions with model membranes at sub-nanomolar concentration.