Undesired Usage and the Robust Self-Assembly of Heterogeneous Structures
Figure 8: Non-stoichiometric concentrations can suppress undesired aggregation in irreversible colloidal assembly. From A. Murugan, J. Zou & M.P. Brenner, "Undesired usage and the robust self-assembly of heterogeneous structures," Nature Communications 6:6203 | doi:10.1038/ncomms7203. Reprinted by permission from Macmillan Publishers Ltd:Nature Communications ©2015.
Prof. Michael Brenner and colleagues from SEAS and Kavli Institute for Bionano Science and Technology have published an article in the latest issue of Nature Communication which describes their study of the spontaneous assembly of structures made of many kinds of components, inspired by multiprotein complexes in biology and recent successes in synthetic DNA tile and colloidal self-assembly.
The major challenge with achieving high assembly yield is eliminating incomplete or incorrectly bound structures. The reserachers found that such undesired structures rapidly degrade yield with increasing structural size and complexity in diverse models of assembly, if component concentrations reflect the composition (that is, stoichiometry) of the desired structure. But this yield catastrophe can be mitigated by using highly non-stoichiometric concentrations. The results of this study support a general principle of 'undesired usage' - concentrations of components should be chosen to account for how they are 'used' by undesired structures and not just by the desired structure. This principle has a potential to improve synthetic assembly methods, but also raises new questions about expression levels of proteins that form biological complexes such as the ribosome.