A 3D-printed brain-like environment developed by TU Delft allows neurons to grow as they do in real brains. The environment includes tiny nanopillars, which mimic a soft, brain-like structure and extracellular matrix fibres in the brain. The model enables new insights into how neurons form networks. It can also serve as and tool to be able to alter this process, opening up opportunities in neurological diseases such as Alzheimer's, Parkinson's and autism spectrum disorders.
Neurons are specialised cells in the nervous system that transmit electrical and chemical signals. They form the basis of brain function and nerve communication, and are also considered the building blocks of the brain. The cells specialise in transmitting information to other nerve cells, muscle cells and glandular cells.
Neurons respond to the stiffness and shape of their environment
Like many other cells, neurons respond to the rigidity and shape of their environment. However, a traditional petri dish is hard and flat, while the environment in the brain is soft and fibrous. This can therefore affect the functioning of neurons in a petri dish. Angelo Accardo's team developed 3D-printed brain-like environments to mimic the brain environment as closely as possible.
environment includes nanopillars, each one a thousand times thinner than a human hair. By adjusting the width and height of the pillars, the researchers were able to tune their sliding modulus. Shear mode is a mechanical property that cells perceive when crawling over micro- or nanostructures.
Neurons trick
Accardo explains, "This tricks the neurons into thinking they are in a soft, brain-like environment, although the material of the nanopillars themselves is rigid. Because they bend as neurons crawl over them, the nanopillars not only simulate the softness of brain tissue, but also provide a 3D structure for neurons to cling to, just like the extracellular matrix fibres in real brain tissue."
model was tested by the researchers with three types of neurons, taken from mouse brains or human stem cells. In this, the neurons grew in all directions on regular petri dishes. On the 3D-printed nanopillars, however, they grew in organised patterns, forming networks at certain angles.
Growth cones behave differently
Accardo team's research also shows that the growth cones of neurons behave differently thanks to the presence of nanopillars. "Normally, the ends of growth cones spread out flat," Accardo said. "But on the nanopillars, the growth cones formed long, finger-like protrusions, with which they explored in all directions, not only in a plane, but also in 3D, like in real brains."
Also shows that neurons on nanopillars mature faster. Cells showed more signs of maturation adar than on flat surfaces such as a petri dish. George Flamourakis, first author of the study, explains: "So the model not only influences how neurons grow, but also encourages them to mature."
Accardo points out that using a gel as a soft environment is not the answer. "The problem with gels like collagen is that they can vary from batch to batch and have no geometric properties," says Accardo. "Nanopillars combine the best of both worlds: a soft environment with nanoscale structures that are consistent and reproducible."
Author: Wouter Hoeffnagel
Image: aziz enn via Pixabay
