A force to reckon with

Evolution has had billions of years to tweak the proteins that make life possible, producing a myriad of specialized structures that can rapidly fold and self-assemble in order to execute their biological functions. Chemists are racing to catch up with nature’s achievements. 

With funding from the King Abdulaziz City of Science and Technology, researchers led by Anne-Sophie Duwez, at the University of Liège in Belgium, have demonstrated that man-made ‘foldamers’ exhibit physical characteristics that can match or even outperform those of naturally occurring proteins. 

Oligorotaxanes are a class of foldamers that feature an extended ‘dumbbell’ shape, which is threaded through a series of ring-like chemical groups. These molecules can potentially be incorporated into sensors that respond to mechanical or electronic signals, or into devices that selectively release a drug or other cargo in response to an external stimulus, but their physical properties have not yet been fully defined. 

Duwez and her colleagues used atomic force microscopy (AFM) to measure the force generated by these polymers as they are unfolded and then allowed to refold. AFM employs a tiny probe that can be used to physically manipulate objects at the molecular scale. For this study, the researchers tethered oligorotaxanes to a solid surface, and then poked and prodded them with an AFM probe that had been chemically modified to form a strong bond with the oligorotaxane. This allowed them to directly quantify the forces being generated by the polymer strands in real-time as they were forcibly extended and allowed to contract. 

Their results showed that the structures formed by these molecules are both remarkably durable and highly resilient. After stretching out the oligorotaxanes with strong forces, they allowed them to relax and resume their naturally preferred folding arrangement. 

Remarkably, this happened within microseconds — under certain conditions, refolding happened at time-scales that were hundreds of times faster than typically occurs with natural proteins. The authors attribute the robust properties of the polymers to their interlocking structure, which imposes strong physical constraints that prevent the molecules from becoming overextended to the point of irretrievable deformation. 

There is considerable excitement surrounding the use of custom-made nanomaterials for drug delivery, molecular detection and other applications. The discovery that oligorotaxanes can exhibit mechanical properties superior to their natural counterparts should encourage researchers looking to maximize the performance of their biologically inspired molecular devices.

1. Sluysmans, D., Hubert, S., Bruns, C.J., Zhu, Z., Stoddart, J.F. & Duwez, A.-S. Synthetic oligorotaxanes exert high forces when folding under mechanical load. Nature Nanotechnology 13, 209–213 (2018). | article