Detection of Polypeptide Conformational Transitions in Solution via Sound Velocity and Optical Rotation

Of the many different core-shell particles being designed for drug delivery, protein sequestration, and other applications, polypeptide-coated silica is among the most promising. The combination of a configurable, chiral surface and a wide spectrum of surface moieties is difficult to match using conventional polymers. A model system for such polypeptide-silica composite particles (PCPs) has been constructed by covalent attachment of poly (ε-carbobenzyloxy-L-lysine) (PCBL) to silica microbeads. PCBL exhibits a reversible coil-helix transition when dissolved as a pure polymer in m-cresol, but the use of conventional optical methods (e.g., circular dichroism) to confirm such a transition for particles tethered to silica beads is confounded by solvent opacity and strong scattering. Sound velocity measurements provided comparable results to the conventional methods, such as optical rotation, but allows for optically active solvents and strongly scattering samples to be more easily measured. The combination of these two methods provides a new way to understand polypeptide transitions in complex environments and real-world formulations.