Are Neutral Polyzwitterions Really Neutral? Charge Symmetry Breaking!

Determination of the net electric charge of a macromolecule dispersed in aqueous media continues to remain elusive. The primary reason for this is the lack of ability to explore the local dielectric constant accompanying water organization in the vicinity of ion-pair formation from a charged monomer and its counterion. In efforts to directly address this fundamental question, the design of our single-molecule experiment is as follows. Choosing a neutral polyzwitterion, where one charged group of the zwitterionic monomer is closer to the chain backbone and the other oppositely charged group of the monomer is distal from the chain backbone, we have conducted single-molecule electrophoresis through a solid-state nanopore. Surprisingly, the neutral polymer is not silent to the electric field, but moves in one direction, but not in the opposite direction. The direction of the molecule's movement shows that the charge of the zwitterion monomer closer to the backbone is more masked by counterion binding in comparison with the distal charge. We attribute this charge symmetry breaking to a gradient in the local dielectric constant. We suggest a method to quantify this effect by combining our experimental results and our translocation theory based on Fokker-Planck formalism. This discovery that even a neutral polar polymer can function as a polyelectrolyte near an electric field opens a new avenue of understanding of how macromolecules move in crowded environments.