Illuminating the Reaction Pathways of Viromimetic Assembly.
The coassembly of well-defined biological nanostructures relies on a delicate balance between attractive and repulsive interactions between biomolecular building blocks. Viral capsids are a prototypical example, where coat proteins exhibit not only self-interactions but also interact with the cargo they encapsulate. In nature, the balance between antagonistic and synergistic interactions has evolved to avoid kinetic trapping and polymorphism. To date, it has remained a major challenge to experimentally disentangle the complex kinetic reaction pathways that underlie successful coassembly of biomolecular building blocks in a noninvasive approach with high temporal resolution. Here we show how macromolecular force sensors, acting as a genome proxy, allow us to probe the pathways through which a viromimetic protein forms capsids. We uncover the complex multistage process of capsid assembly, which involves recruitment and complexation, followed by allosteric growth of the proteinaceous coat. Under certain conditions, the single-genome particles condense into capsids containing multiple copies of the template. Finally, we derive a theoretical model that quantitatively describes the kinetics of recruitment and growth. These results shed new light on the origins of the pathway complexity in biomolecular coassembly.
Physical Chemistry and Soft Matter, Wageningen University & Research , Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Hande E
HE
Cingil
Physical Chemistry and Soft Matter, Wageningen University & Research , Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Emre B
EB
Boz
Soft Matter Physics, Huygens-Kamerling Onnes Laboratory, Leiden University , PO Box 9504, 2300 RA Leiden, The Netherlands.
Giovanni
G
Biondaro
Physical Chemistry and Soft Matter, Wageningen University & Research , Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Renko
R
de Vries
Physical Chemistry and Soft Matter, Wageningen University & Research , Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Martien A
MA
Cohen Stuart
Soft Matter Physics, Huygens-Kamerling Onnes Laboratory, Leiden University , PO Box 9504, 2300 RA Leiden, The Netherlands.
Daniela J
0000-0002-2221-6473
DJ
Kraft
Theory of Polymers and Soft Matter, Eindhoven University of Technology , PO Box 513, 5600 MB Eindhoven, The Netherlands.|Institute for Theoretical Physics, Utrecht University , Leuvenlaan 4, 3584 CE Utrecht, The Netherlands.
Paul
P
van der Schoot
Physical Chemistry and Soft Matter, Wageningen University & Research , Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Joris
0000-0001-6532-4514
J
Sprakel