ATP drives the supramolecular tango
A first of its kind synthetic molecule assimilates bio-mimetic supramolecular growth behavior on exposure to biological co-factors.
The paper in Nature Communications is here: https://go.nature.com/2Gtpz6M
Imagine a world without hope, its entities confined to their monotonous routines. Suddenly, they start noticing a distant rumbling. What is it? they wonder. It starts becoming more and more evident. “Music!” yelled somebody and things were never the same. Each atom in their body begins to respond, and suddenly they are overcome by this irresistible need to twist. As more and more poured in to examine this strange phenomenon they could not help but join in. “Who's who was buying it all over town, You see them, a-squirming and a-worming and a-twistin' around”.
No, dear reader this is not a scene from a Broadway musical, on the contrary this is a metaphorical account of Mishra et al’s recent work published in Nature Communications. They have designed, in their lab, a supramolecular system that dances on the tunes of Adenosine triphosphate (ATP) and much like the participants in the revelries accounted above, these molecules are hooked!
The principal molecule described in this study is a oligo(p-phenylenevinylene) derivative, functionalized with dipicolylethylenediamine-zinc complex (DPA–Zn) as phosphate receptors. These molecules when exposed to biological cues such as ATP, undergo a conformational shift and start arranging into a helical aggregate. These aggregates now act as nuclei for incoming monomers that, in presence of ATP, start extending the existing nuclei into longer supramolecular helices. Incredibly, the temporal and morphological profile for growth is controlled selectively by ATP. The study also demonstrates exotic out-of-equilibrium scenarios in which a clear supramolecular control can be established. These characteristics are impactful as this supramolecular behaviour is akin to biologically occurring cytoskeletal proteins such as actin, which have long been a scientific hurdle to synthetically replicate owing to its bio-molecular selectivity and rigid temporal control. This report represents the first effort in this direction.
Deciphering this supramolecular tango was a challenging task and was alleviated by intelligent design of experiments. Study of initial intermediates of nucleation has traditionally been quite challenging owing to their diminishing stabilities even over few minutes. Mishra et al analysed the ATP driven supramolecular growth profile by various spectroscopic tools revealing the key intermediates in the initial time frames of ATP binding, leading to insights into nuclei formation. These insights help the authors in rationalizing a lucid growth mechanism of their aggregates. Furthermore the coupled existence of ATP selectivity and nuclei elongation was proven by astute seeding experiments and complimented by detailed theoretical simulations.
Biological cues controlling synthetic systems, not only morphologically but also temporally, opens new and exciting avenues. How about temporally coupled networks of aggregating systems? A step further, possibility of biologically interactive synthetic networks? The answer seems to be: Follow the music!