Biophysics: delayed supply of building blocks facilitates assembly

The ability to self-organize is a key feature of biological systems and is widely found in nature: Small building blocks that autonomously assemble give rise to macromolecules such as the cell nucleus, virus capsids, or complex cellular structures – often in compartmentalized environments which specifically facilitate or control such processes. Understanding the principles of this self-assembly also guides recent developments in synthetic biology and nanotechnology. LMU biophysicists Severin Angerpointner, Richard Swiderski, and Professor Erwin Frey have developed a new theoretical model which demonstrates that the delayed supply of building blocks can improve the effectiveness of the self-assembly of complex structures in compartmentalized systems.

“Intuitively, one would expect that a rapid resupply of building blocks would be most conducive to the growth of structures,” says Frey. “We find, however, the opposite to be the case: Slow supply from a reservoir increases the yield and shortens the time for complete assembly.” As the model shows, this prevents the formation of too many ‘assembly nuclei’ simultaneously, which would take resources from each other, and favors the maturing of existing structures: “If the exchange is too fast, nothing gets done properly. If it is too slow, the system starves,” says Frey. “In between, there is an optimal delay range: Structures that have already started to form are prioritized for growth and are able to mature quickly and fully.”

The effect is general, emphasize the researchers: It occurs in different geometries and reaction schemes and requires no fine-tuning of molecular binding energies. “Our work furnishes experimentally testable predictions and design principles for synthetic and biological systems. As such, it has greater relevance beyond the specific model,” notes Frey.

Severin Angerpointner, Richard Swiderski, Erwin Frey: Delay-facilitated self-assembly in compartmentalized systems. PNAS 2025