Interface Flexibility: Scientists Discover Key Mechanisms Drive the Formation of Molecular Networks

Covalent bonds are a widely understood phenomenon in which atoms of a molecule are joined by covalent electron pairs. But essentially, molecular patterns can also be connected via weaker, more dynamic forces that produce supramolecular networks. These can self-assemble from early molecular clusters or crystals and grow into a large, stable architecture.

Supramolecular networks are essential to maintaining the structure and function of biological systems. For example, to “eat,” cells rely on a hexagonal supramolecular network that self-assembles from the three-arm protein clathrin units. The clathrin network forms bubbles around nutrients and brings them into the cells. Similarly, a protein called TRIM5A forms a hexagonal lattice that forms around the HIV virus, helping to disrupt replication.

“This hexagonal network structure is essentially ubiquitous, even viewable at a beehive macroscale, for example,” said the head of the EPFL’s Department of Engineering Programmable Biomaterials Lab (PBL). One Maartje Bastings explains.

The latest study published in Nature Chemistry uses researchers from PBL and Bio-and Nano-Instrumentation (LBNI) led by Georg Fantner to use nano-engineering DNA strands with three-point star-shaped nano-engineering DNA strands. I used it for another star shape. Factors that control the formation of crystalline supramolecular networks.

In the process, they discovered that they “define parameters” which are even more important than chemical bond strength or number.

“Interface flexibility always wins.”

Similar to human DNA, the composition of three-point star DNA molecules was varied by the sequence of nucleotides, affecting the strength (affinity) of interaction with adjacent molecules. However, in this study, the researchers introduced additional variables. Local and global flexibility of the arms could be adjusted through subtle variations in the length of the strands that make up each of the three arms of the monomer.

Using a high-speed nuclear power microscope, the team has DNA stars with short rigid “arms” organized into a stable hexagonal network, but people with longer, more flexible arms form a larger network I observed that I couldn’t do it.

Simulations reveal that short arms are almost four times more likely to be placed in parallel shapes that help connect with other molecules more, and that longer arms tend to be too far apart to create a stable connection It has become. Researchers called this variation interface flexibility.

“The interface where two molecules come together is rigid. If one is flexible, the molecule is less likely to maintain a connection. Bond strength is not important. Interface flexibility always wins. Basting says.

Interestingly, the researchers also showed that interface flexibility can be fine-tuned. Flexible molecules were able to restore local stiffness with sufficient binding interfaces to support network growth, while maintaining the overall size of the molecule.

“This means that even globally flexible monomers can grow into a network if the flexibility of the interfaces at the point of binding is controlled,” Bastings sums up.

Build or destroy

Bastings says the study could change the way scientists design proteins and other molecules for self-assembly, creating new opportunities for cell nanotherapy.

Targeted approaches can focus, for example, on stiffness in the design of new supramolecular networks from proteins. or inducing flexibility for strategic failure or prevention of unwanted networks, such as amyloid plaques seen in connection with Alzheimer’s disease. She also foresees applications in spironics where self-organization of well-defined nanoscale networks could help build next-generation electronics.

She praises the achievements of her lab student initiatives and LBNI collaborators. And she will never forget to give justified recognition to humble DNA molecules.

“Advances in interdisciplinary DNA nanotechnology and in controlling properties at the atomic level have made DNA a mainstay for extracting DNA from the genomic context and discovering global physical interactions such as interface flexibility. It’s now possible to convert it.”