Single-Molecule Force Spectroscopy on Synthetic Helical Nanoarchitectures

Inspired by the many folded conformations of the molecular machineries in nature, chemists have been developing the syntheses of artificial folded molecular architectures, namely foldamers. The investigation of these molecules using AFM-based Single Molecule Force Spectrosocopy (SMFS) allows the elucidation of both mechanochemical properties and conformational dynamics on the unimolecular scale in solution. The stepwise synthesis of aromatic oligoamide-based foldamers was designed to produce well-defined helically-folded molecular architectures. A PEO tether was coupled to one end of the foldamer. SMFS pulling experiments on this system yielded specific and reproducible force-extension patterns characteristic of single foldamers. Those patterns were further analyzed to determine unfolding forces and dynamics as well as to propose mechanistics hypotheses of the unfolding process. Several helical foldamers presenting variable lengths were considered. The force values measured for those foldamers are higher than those previously measured in natural biopolymers showing a high stability under a load and a propensity for the development of emergent properties. In addition, the increased stability of these aromatic oligoamide foldamers was confirmed by the observation of almost instantaneous reversibility of the unfolding under load.