Researchers unlock new level of precision in supramolecular materials

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Researchers unlock new level of precision in supramolecular materials

Giant 'giga' assemblies of different molecules enable novel materials, supercharge neurons

• Link to: Northwestern Now Story

EMBARGOED UNTIL 2 P.M. EDT (U.S.) ON THURSDAY, OCTOBER 1, 2026

• Self-assembling molecules form thread-like supramolecular polymers that easily reach or exceed the dimensions of cells
• Scientists can precisely control thread length and their chemical segments to create structurally stable assemblies containing domains with positive and negative electrical charges
• The structures are formed using a strategy the scientists have named 'self-capping supramolecular polymerization'
• The precise arrangement of segments transforms how materials interact with living cells

EVANSTON, Ill. - Northwestern University scientists have developed remarkably long, precisely patterned molecular threads that could open new possibilities for designing advanced materials. The scientists also discovered these threads - called supramolecular polymers - can dramatically enhance brain cell activity.

The study was published today (Oct. 1) in the journal Science.

Built from self-assembling molecules, the longest threads reach dimensions greater than the diameter of a cell. By molecular standards, they are giant - roughly 100 times more massive than even very large conventional polymers and the largest known proteins in biology. Yet despite their enormous size, scientists can precisely control their lengths and organize them into chemically distinct segments with defined dimensions carrying opposite electrical charges.

That precision also produced an unexpected biological effect. In cell culture studies, the structures enhanced the growth and organization of neurons and increased synapse formation.

The findings introduce a new way to use self-assembly to build highly controlled supramolecular materials with precise physical arrangement of chemical structures. Ultimately, the work could inform materials' design for a range of applications, including biomaterials for regenerative medicine.

"These structures represent a breakthrough in materials design, and we already discovered one useful application: their superbioactivity toward neurons, which will bring new opportunities in regenerative medicine," said Northwestern's Samuel I. Stupp, who led the study. "Typically, when we design a regenerative material, we add biological signals, designed to activate cell receptors. Here, the material itself becomes highly bioactive simply through the precise organization of electrical charges and its dynamic behavior. That introduces a very different way of thinking about how materials can communicate with cells."

A pioneer in self-assembling materials and regenerative medicine, Stupp is the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine, Neuroscience and Biomedical Engineering at Northwestern, where he has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Northwestern University Feinberg School of Medicine. He also directs the Center for Regenerative Nanomedicine. Three members of the Stupp laboratory are co-primary authors of the paper: postdoctoral fellow Michael Dore and graduate students Simon Egner and Madison Strong.

Bringing precision to self-assembly

The new study builds on Stupp's long history working with supramolecular materials, dynamic structures that form when molecules spontaneously organize through weak, reversible interactions. While conventional polymers, like plastics, hold together using strong, permanent chemical bonds, supramolecular polymers are dynamic, allowing their components to move and reconfigure, which generates life-like properties in synthetic systems. Supramolecular polymers exist in all living organisms, where they perform essential functions and hold promise for future soft matter technologies.

That flexible, dynamic nature can be useful for interacting with living cells in biomedical applications, but it also makes the structures difficult to control. Scientists can design the individual molecular building blocks but then struggle to control how long the resulting structures grow and how they organize their chemical components.

Stupp's team overcame that limitation by using novel designs of molecules and carefully controlling their assembly process. With this strategy, the researchers could dictate the threads' lengths and keep them uniform. Once the growth stopped, the structures maintained their precise lengths rather than fusing together or rearranging.

"We let these filaments sit in a test tube for months, and they surprisingly didn't change," Stupp said. "They remained the same length and retained their segmented structures."

Grow, stop, grow again

Stupp and his team traced that unusual ability to a previously unknown process his laboratory calls "self-capping supramolecular polymerization." As a thread grows, flexible portions at the ends remain highly dynamic and, at proper temperatures, allow new molecules to join in a synchronized manner. Once the available building blocks are consumed, those flexible portions fold over and protect the ends. This effectively shuts down further growth by preventing threads from fusing together or undergoing "Ostwald Ripening," a process in which smaller structures disappear while larger ones grow.

"To make them longer and longer, we just kept adding new molecules," Stupp said. "The new molecules stick with strong noncovalent bonds to the growing thread and elongate the assembly, which led to a breakthrough in terms of size control.

"The collective molar mass of their noncovalently bonded monomers reaches billions of daltons, and thus they are 'giga-assemblies.' These are the largest supramolecular polymers ever made with this degree of precision. Once the monomer is fully consumed, they finish growing and their dimensions remain stable."

Approximately the size of one proton or neutron, a dalton is a tiny unit that scientists use to measure the mass of molecules and atoms. More than a billion daltons is enormous by molecular standards. For comparison, the largest common polymers of plastics have molar masses in the range of 10 million daltons, and the largest proteins in nature reach approximately 3 to 5 million daltons.

Researchers can later restart growth by supplying more building blocks. By adding different types of molecules in sequence, the researchers can create precisely defined segments with different chemical properties. In the study, Stupp and his team created threads with positively and negatively charged segments. Because opposites attract, the researchers expected the threads to clump together. Instead, they remained stable in water because the "capping" mechanism prevented the assemblies from fusing together.

Small anchor, big difference

To explore how the pattern of electrical charges might interact with living cells, Stupp and his team turned to neurons, which carry a strong negative charge. The team exposed several threads with different designs to cellular cultures containing cortical neurons.

"The first thing we did was make a structure with only positively charged segments, and it basically killed the neurons," Stupp said. "Then, we tried a structure with only negatively charged segments, and nothing happened because the neurons repelled the materials."

When Stupp's team used supramolecular assemblies with randomly mixed positive and negative charges, the neurons didn't respond in a notable way. But then the team designed a thread with the breakthrough polymerization strategy comprising a small positively charged segment sandwiched between two negatively charged segments of different lengths. Something interesting and unexpected occurred.

The small positive region anchored the thread to the negatively charged surface of a neuron. Repelled by the neuron's negative charge, the thread's negative segments remained highly mobile and in constant motion since they could not escape.

"When we used only positively charged segments, they suffocated the neuron and killed it," Stupp said. "But with only one positively charged segment surrounded by negative ones, it couldn't do that anymore. And the negative segments, which ordinarily couldn't get near the neuron, were forced to stay near it because they were anchored."

Neurons grow and spring to life

Neurons treated with the precisely segmented threads grew longer neurites - the long projections neurons use to communicate with other cells. The treated neurons also formed more elaborate branches, gaining the ability to connect with neighboring cells.

"The neurons matured to an amazing level," Stupp said. "They grew long and highly branched neurites, which is how they can start making synaptic connections in the brain and in the spinal cord."

After just seven days, treated neurons were much more active than untreated neurons. When stimulated, treated neurons produced a calcium response - a sign of neuronal activity. Their overall calcium activity was four times greater. And, after 14 days, treated neurons formed more synapses than untreated neurons.

Stupp and his team saw another striking effect in cultures of human neural progenitor cells, which are immature cells that can develop into neurons. Although these cultures typically grow in flat layers, the cells instead organized into raised, three-dimensional clusters connected by axons. This organization resembled aspects of the brain's white and gray matter, where somas are separated from axons.

No signals required

Perhaps most surprisingly, the molecular threads produced these effects without carrying biological signals specifically designed to encourage neurons to grow. Stupp posits the negatively charged segments recruit specific proteins already present around the cells that help neurons survive, grow and communicate. These proteins, called neurotrophic factors, have positively charged domains. Stupp's team also found laminin - an important protein that holds tissues together and has positively charged domains - accumulating along the supramolecular threads near neurons.

Stupp hypothesizes that the interplay between attraction and repulsion causes the threads' negative segments to rapidly move toward and away from the neurons in a "tapping" motion. Proteins recruited by the negative segments may be drawn toward receptors on the neurons, while electrostatic forces push the segments away. This repeated tapping, occurring on millisecond timescales, could help enhance biological signaling. A live cell movie included in the Science paper has captured this phenomenon.

Beyond neurons, Stupp says the new polymerization strategy could eventually enable scientists to build long molecular structures containing many carefully positioned chemical segments. That could open opportunities to create new materials and devices with features that extend over very long distances.

"We discovered something we had never seen before in chemistry or in biology," Stupp said. "This work gives us a new level of control over supramolecular materials. In the future, we can imagine creating many segments with different properties. The unknown functions of these structures are likely to be as surprising as the superbioactivity observed on neurons. We're just beginning to imagine the possibilities.

The study, "Precise length and charge segmentation of billion-dalton supramolecular polymers," was supported by the U.S. National Science Foundation, the Center for Regenerative Nanomedicine, the Potocsnak Family and Fifth Generation Distilled Spirits Inc. Dore received support from the American Australian Association and Strong received support from the National Institutes of Health and a Ryan Fellowship from the International Institute of Nanotechnology at Northwestern.

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Samuel I. Stupp

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Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine, Neuroscience and Biomedical Engineering

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