This scanning electron micrograph shows the self-assembled superstructures (colored regions) formed by the surprising dynamics of molecules containing peptide and DNA segments. The superstructures are embedded in a matrix of peptide filaments. Image: Mark McClendon and Ronit Freeman.
This scanning electron micrograph shows the self-assembled superstructures (colored regions) formed by the surprising dynamics of molecules containing peptide and DNA segments. The superstructures are embedded in a matrix of peptide filaments. Image: Mark McClendon and Ronit Freeman.

Scientists have been searching for ways to develop materials that are as dynamic as living things, with the ability to change shape, move and change properties reversibly. Now, with nature as their inspiration, researchers at Northwestern University have developed soft materials that can autonomously self-assemble into molecular superstructures and then disassemble on demand, changing their properties as they do so. This opens the door for novel materials in applications ranging from sensors and robotics to new drug delivery systems and tools for tissue regeneration.

These highly dynamic new materials, which are described in a paper in Science, have also provided unexpected biological clues about the brain micro-environment after injury or disease.

“We are used to thinking of materials as having a static set of properties,” said Samuel Stupp, director of Northwestern’s Simpson Querrey Institute and co-corresponding author of the paper. “We’ve demonstrated that we can create highly dynamic synthetic materials that can transform themselves by forming superstructures and can do so reversibly on demand, which is a real breakthrough with profound implications.”

To create the material, Stupp and his postdoctoral fellow Ronit Freeman, now an associate professor at the University of North Carolina, Chapel Hill, developed some molecules composed of peptides (short strings of amino acids) and other molecules composed of peptides and DNA. When placed together, these two types of molecules co-assembled to form water-soluble nanoscale filaments.

If some of those filaments contained complementary DNA sequences that could join together, the resulting double helices ‘jumped out’ of their filaments to organize the unique complex superstructures. This left behind the molecules without DNA to form simple filaments.

The DNA superstructures, containing millions of molecules, look like twisted bundles of filaments that reach dimensions on the order of microns in both length and width. The resulting material is initially a soft hydrogel, but becomes mechanically stiffer as the superstructures form. The structures are hierarchical — meaning they contained ordered structure at different scales. Nature does this very well — bone, muscle and wood are hierarchical materials — but such structures have been very difficult to achieve in synthetic materials.

Even better, the researchers found that when they added a simple DNA molecule able to disrupt the double helices that interconnect the filaments in the superstructures, the bundles came undone, and the material returned to its initial simple structure and softer state. Another type of molecule could then be used to reform the superstructures to make the material stiffer again. That sort of reversibility had never been achieved before.

To better understand how this process worked, Stupp connected with Luijten, a computational materials scientist at Northwestern. Luijten, with his graduate student Ming Han, developed simulations that helped to explain the mechanics behind how and why the bundles formed and twisted. In such simulations, Han and Luijten could examine how each part of the designed molecules governed the creation of the superstructures. After extensive computation – each calculation took weeks on Northwestern’s Quest supercomputer – they found that the molecules did not need DNA to bundle together but could be formed in principle by many other pairs of molecules that interact strongly with each other.

“Based upon our understanding of the mechanism, we predicted that just positive and negative charges on the surface of the filaments would be sufficient,” Luijten said. That means such superstructures could be created without the presence of DNA, in a completely synthetic material.

Stupp and his lab members then created the same material using just peptides. When they used peptides with opposite charges in a specific architecture that mimics DNA complementarity, they found that the peptides would self-assemble into superstructures that were reversible when the charges were neutralized.

The potential uses for these materials extend into medicine and beyond. A complex therapy with proteins, antibodies, drugs and even genes could be stored in the superstructures and released into the body on demand as the hierarchical structures disappear. Scientists could also search for new materials in which the reversible superstructures induce changes in the material’s electronic, optical or mechanical properties, or even color and light emission, Stupp said.

“Now that we know this is possible, other scientists can use their imagination and design new molecules in search of these new ‘dynamic’ materials that reorganize internally on demand to change properties,” he said.

The new materials also led the researchers to a biological discovery. They took astrocytes — cells in the brain and spinal cord associated with neurons — and placed them on the new materials. Astrocytes are important because, when the brain or the spinal cord are injured or diseased, they acquire a specific shape known as the ‘reactive phenotype’ and produce scars that are dense fibrous networks. In the healthy brain, astrocytes have a ‘naïve phenotype’ and a different shape.

Interestingly, when the researchers placed astrocytes on the material made from only simple filaments, the astrocytes had a naïve phenotype, but when the superstructures formed they became reactive. The astrocytes then reverted back to the naïve phenotype when the hierarchical structure disassembled. This discovery links the architecture of the cell’s microenvironment to the critical changes of phenotype that occur when the central nervous system is diseased or injured.

Biologists recently discovered that it was possible to revert reactive astrocytes to their naïve state by transplanting them into healthy subjects who do not have injuries. Stupp and his collaborators have now shown that their new material can also trigger these phenotype transformations in brain cells.

“The cell responded to the structure of the material in its environment,” Stupp said. “It gives us new ideas on how to undo the scars in injured or diseased brain and spinal cord.”

This story is adapted from material from Northwestern University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.