Investigating Sequence-Conformation Relationship Using Polypeptoids: A Single-Molecule Force Study

The effects of sequence on the structure and dynamics of a polymer chain are of interest to many research fields, such as block copolymer self-assembly or protein physics. Single-molecule force experiments offer a unique and unobstructed approach to studying these effects by extracting key polymer physics parameters of intramolecular electrostatic and hydrophobic interactions that influence the global chain structure. Here, we present the use of polypeptoids, an analog of polypeptides, as a model to isolate and investigate the effect of charge sequence on polymer conformations by designing simple sequences with only two types of side chains: neutral hydrophilic and charged. Using high-resolution single-molecule magnetic tweezers that can access subpicoNewton forces, we found a clear trend in the effect of net charge and charge spacing on the conformational behaviors of the polypeptoids. Overall, this work elucidates the electrostatic sequence-conformation relationship of polymers, which better understanding of the physical principles of biopolymers' in vivo behaviors and guide the design of new polymeric materials.