Supramolecular networks are standard and form similarly to crystals, starting from a small point and growing based on interactions between their parts. Strong and directed interactions typically control their growth, while flexible structures are more prone to defects. Large molecules with multiple binding sites can be flexible, but the impact of this flexibility on network formation hasn’t been well-studied.
Clathrin networks transport nutrients into cells by creating bubbles around them. Similarly, the TRIM5a protein forms hexagonal lattices around HIV viruses, disrupting their replication. This hexagonal structure is efficient and common in nature, like beehives.
EPFL scientists discovered a new property called interface flexibility, which controls how molecules self-organize into crystalline networks. This discovery could revolutionize the design of synthetic molecules for nanoscale networks.
Maartje Bastings, head of the Programmable Biomaterials Lab (PBL) in EPFL’s School of Engineering, said, “This hexagonal network structure is omnipresent in nature – you can even see it at the macroscale in beehives, for example.”
For their latest study, Georg Fantner’s researchers from the PBL and the Laboratory for Bio- and Nano-Instrumentation (LBNI) used nanoengineered DNA strands in a three-point star shape to isolate and examine the different factors controlling crystalline supramolecular network formation. They discovered a “defining parameter” even more important than chemical bond strength or number.
Using high-speed atomic force microscopy, they found that DNA stars with shorter, rigid arms formed stable hexagonal networks, while those with longer, more flexible arms did not. This is due to interface flexibility: rigid arms connect better and form stable networks, while flexible arms tend to spread apart.
This finding highlights that interface flexibility is crucial for network formation rather than just binding strength. Even flexible molecules can form networks if their binding points are made rigid.
Maartje Bastings believes this discovery could transform the design of proteins and molecules for self-assembly, opening new opportunities for cellular nanotherapies and advancements in electronics. She credits the success to her students and collaborators, emphasizing the role of DNA nanotechnology in understanding global physical interactions.
Journal Reference:
- Caroprese, V., Tekin, C., Cencen, V. et al. Interface flexibility controls the nucleation and growth of supramolecular networks. Nat. Chem. (2025). DOI: 10.1038/s41557-025-01741-y
