Chemically engineered synthetic lipid vesicles for sensing and visualization of protein - bilayer interactions.

From pathogen intrusion to immune response, 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 (~5-15X) than those for low molecular weight proteins. Through mass spectrometry (MS), we found that only six out of sixty (10%) lysine groups present in bovine serum albumin (BSA) were accessible to membrane of the vesicles. Finally, a "sphere-shell" model representing protein-vesicle complex was used for evaluating contribution of the van der Waals interactions between proteins and vesicle. Our analysis points toward 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, semi-quantitative way of detecting biomolecules and their interactions with model membranes at sub-nanomolar concentration.