Programming Synthesis and Assembly of Viral Parts in 2D Compartments

The assembly of protein machines, such as viruses, in cells is precise, rapid, and coupled to protein synthesis with regulation in space and time. Reconstitution of this process outside the cell could provide means to decipher viral assembly lines and facilitate the discovery of drugs that disrupt assembly with therapeutic potential. We present quasi-2D silicon compartments that enable programming of protein assembly lines by local synthesis from surface-immobilized synthetic gene brushes¹. Local synthesis and surface capture of complexes provide high assembly yield and sensitive detection of spatially resolved assembly intermediates. The 3D geometry of the compartment and the 2D pattern of gene brushes were found to dictate the yield and mode of assembly steps. This methodology enables deciphering, reconstructing, and designing biological machine assemblies, as well as combating pathogens.

Reference:

Vonshak, O.; Divon, Y.; Förste, S.; Garenne, D.; Noireaux, V.; Lipowsky, R.; Rudorf, S.; Daube, S. S.; Bar-Ziv, R. H. Programming multi-protein assembly by gene-brush patterns and two-dimensional compartment geometry. Nat. Nanotechnol. 15, 783–791 (2020). https://doi.org/10.1038/s41565-020-0720-7