| AVS 61st International Symposium & Exhibition | |
| Biomaterial Interfaces | Monday Sessions |
| Session BI+AS-MoM |
| Session: | Biomolecules & Biomaterials Interfaces |
| Presenter: | Joe Baio, Oregon State University |
| Authors: | J.E. Baio, Oregon State University D. Schach, University of Chicago M. Bonn, Max Planck Institute for Polymer Research, Germany T. Weidner, Max Planck Institute for Polymer Research, Germany |
| Correspondent: | Click to Email |
GALA peptides (WEAALAEALAEALAEHLAEALAEALEALAA) mimic pH-sensitive viral fusion proteins and are widely touted as a promising route to achieve site-specific delivery of therapeutic compounds. At basic pH, GALA assumes a random coil structure but when lowering the pH to acidic conditions the peptide transitions into an alpha helical structure. In this state, GALA has the ability to penetrate cell membranes and form pores. This mechanism is mainly driven by the change in overall charge of the glutamic acid side chains. One development of GALA mediated drug delivery is the immobilization of these peptides onto Au nanoparticles. Here we demonstrate, using a variety of spectroscopic techniques, that GALA can self-assemble into a protein monolayer on a gold film, linked to the surface via a single cysteine synthesized to the carbonyl terminus. Transmission IR vibrational spectroscopy demonstrates that the addition of this cysteine does not impede the pH transition between a helix and random coil structure in solution. Detailed characterization of the thiol-Au immobilization scheme by X-ray photoelectron spectroscopy illustrates that this single cysteine induced the formation of a well-ordered protein monolayer. To directly observe any pH triggered transition of this protein monolayer, sum frequency generation (SFG) vibrational spectra, at the amide I vibrational band, were collected at four different pH environments. A vibration mode at 1655 cm-1, related to a helical structure, appears when this monolayer is immersed in a buffer at acidic conditions (pH 3 and 5) and then disappears under basic conditions (pH 9 and 12). While the surface immobilization clearly reduces the effective glutamic acid pKa from a bulk solution value of 6 to 5.5, the covalently bound GALA-cysteine monolayer reliably retained the reversible, pH-driven helix-coil transition mechanism. Our findings establish that covalent attachment of GALA via cysteine linkers is a promising route for drug delivery applications and the design of ‘smart’ biological coatings.