Single-Molecule Force Experiments Reveal Effects of Sequence Charge on Polyelectrolyte Conformation*

For sequence-defined polyelectrolytes, modulating their charge location and patterning can significantly alter their physical properties and functionality. This calls for a fundamental understanding of how charge sequence influences polyelectrolyte conformation. Single-molecule force experiments can provide a unique perspective on the polymer sequence-structure relationship through direct probing of polymer structures and interactions. Here, by designing and testing simple charged polypeptoid sequences, we investigate the effect of net charge and charge spacing on the conformational behaviors of a flexible polyelectrolyte. Surprisingly, we see that the peptoid net charge does not significantly affect polymer stiffness (persistence length) and extent (Flory exponent) at low ionic strength. Instead, charge spacing is the primary driver of peptoid conformation in solution. Sequences with shorter charge spacings transition to ideal chain behavior at higher ionic strengths. We find that the theta-point of all charged sequences can be normalized to when their charge spacings are equal to the Debye screening lengths. Overall, this study challenges conventional wisdom on polyelectrolyte conformation and demonstrates the use of single-molecule force experiment as a useful tool to study polymer sequence-conformation relationship.