Bio-inspired supramolecular architecture creates multiple spatial structures autonomously

A research group at the Graduate School of Engineering, Kyoto University, including Professor Itaru Hamachi (at the time of research; currently Specially Appointed Professor at the Institute of Advanced Energy, Kyoto University), Lecturer Ryou Kubota (at the time of research; currently Professor at the Graduate School of Engineering, Kyushu University), Master's Course Student Yuriki Ikuta (at the time of research), Doctoral Course Student Shogo Torigoe (at the time of research), and others developed new methods of supramolecular architecture. In this new structure, artificial molecules assemble multiple types of macro-scale (millimeter to centimeter) complex spatial structures autonomously while repeating "break-and-build", emulating mechanisms of morphogenesis where cells of living organisms create tissues and organs by themselves. The findings were published in Nature Communications.

Molecular self-assembly enables the bottom-up construction of target structures from nanoscale molecular building blocks. However, because conventional systems are governed primarily by thermodynamic control, they tend to form uniform structures. As a result, autonomously constructing materials with the complex spatial organization seen in biological tissues has remained challenging.

During biological development (morphogenesis), concentration gradients of signaling molecules known as morphogens are combined with energy-consuming, dynamically evolving non-equilibrium processes. This guides cells to differentiate and arrange themselves in appropriate locations, ultimately forming highly ordered tissues and organs across scales from the microscopic to the macroscopic.

Inspired by living systems, bottom-up approaches for spatially organizing multiple distinct supramolecular structures on the macroscale within artificial soft materials such as hydrogels have remained largely unexplored. Inspired by biological morphogenesis, the research group demonstrated a new concept termed supramolecular morphological transition.

Specifically, the researchers first prepared a hydrogel composed of self-assembled anionic low-molecular-weight peptide monomers, then allowed a cationic surfactant (DTAC) to diffuse outward from its center.

They discovered that, as the surfactant diffuses, the concentration gradient triggers a non-equilibrium "scrap-and-build" process in which the original peptide fibers are first completely disassembled and then rebuilt into new fibers of different composition while incorporating surfactant molecules.

Coupling these scrap-and-build dynamics with surfactant diffusion generates propagating waves that repeatedly travel outward like ripples.

The researchers found that, as these waves propagate, multiple types of fibers with different compositions and thicknesses autonomously differentiate and ultimately become spatially organized into a striking pattern of four discontinuous concentric rings approximately 14 mm in diameter, forming a supramolecular architecture.

Furthermore, they demonstrated that a one-minute pulse of low temperature (4℃) applied during wave propagation can inscribe a new ring pattern at a specific location. They also showed that simultaneously diffusing two cationic surfactants with different properties from separate locations causes two propagating waves to collide, creating entirely new and complex fusion patterns at the collision boundary.

These results demonstrate that the spatial patterns of supramolecular architectures can be flexibly controlled and modulated through external stimuli and environmental perturbations.

Further development of this autonomous supramolecular architecture technology could enable the creation of next-generation biomaterials and smart soft materials in which microscopic molecular differentiation and macroscopic spatial organization are highly controlled, much like in living tissues.

Kubota said, "This research started from the fascination into the complex 'shape making' of living cells and our wish to reproduce it via gatherings of artificial molecules. I cannot forget even now surprises when unexpected beautiful concentric patterns appeared during experiments and we observed situations where patterns change dynamically under microscopes. We will continue research in the future so that this discovery connects to developments of new functional soft materials as elaborate as living tissues."

Journal Information
Publication: Nature Communications
Title: Supramolecular morphological transition driven by nonequilibrium break-and-build self-organisation
DOI: 10.1038/s41467-026-76336-3