Novel nanowire platform mimics brain tissue to study astrocytes

Scientists have engineered a nanowire platform that mimics brain tissue to study astrocytes, the star-shaped cells critical for brain health, for the first time in their natural state.

Astrocytes are the brain's most abundent and mysterious cells, responsible for regulating communication between neurons and helping to maintain the blood-brain barrier. They are also highly dynamic shape-shifters, someething they do not do on typical petri dishes, leaving major gaps in our understanding of how they operate.

Frustratingly little is known about the stunning diversity of astrocyte morphology and we also don't know much about the molecular machinery behind these shape shifts. They won't take on these shapes on glass, so the question for us was how do we replicate the in vivo shape but in vitro?"

Ishan Barman, co-senior author, Johns Hopkins University bioengineer

By enabling the study of astrocytes in unprecedented detail, the work, led by Johns Hopkins and the National Research Council of Italy, will help us better understand brain function and dysfunction, including what goes wrong in neurodegenerative disorders.

The federally-funded work is newly published in Advanced Science.

Astrocytes underpin brain health. They essentially form the brain's scaffolding. And malfunctioning astrocytes are linked to numerous diseases including Alzheimer's and Parkinson's.

Scientists suspect astrocytes' signature star shape is connected to their various key functions. But those shapes collapse as soon as scientists attempt to study them on typical glass trays under microscopes.

"To truly understand astrocytes we need to replicate their environment," Barman said. "The shape is not random. And if we're not able to recreate it faithfully we're not going to be able to understand the function."

To allow astrocytes to be studied in their true form, the team engineered two breakthroughs.

First they created nanowire mats from glass that mimic the texture of brain tissue while remaining optically transparent. When placed upon this nanowire structure, the astrocytes not only maintain their signature shape, they grow and thrive.

"When grown on nanowire mats, astrocytes regain their star-like morphology, branching and maturing as they do in vivo in the brain," said co-senior author Annalisa Convertino of the National Research Council of Italy.

By combining these nanowires with a new form of imaging that provides high-resolution, 3D views without fluorescent tags or invasive staining, the team was able to capture how astrocytes grow, branch, and change shapes.

"The ability to combine nanowire culture with high-resolution, label-free imaging was critical," said co-first author, Anoushka Gupta, a graduate student in Barman's lab. "It finally allows precise quantification of astrocyte morphology."

The team expects the technique, which could also be used to study other cells, to advance "brain on a chip" technologies including organoids and other next-generation neuroengineering platforms.

"This is a major leap beyond flat culture models and paves the way for a new generation of 'brain on a chip' models," Barman said. "We believe this could herald the beginning of a new way to study neurogenerative diseases, drug effects and brain injuries."

Authors include Pooja Anantha, Anoushka Gupta, Joo Ho Kim, Piyush Raj, Swati Tanwar, Jessica Chen, Luo Gu, all of Johns Hopkins; Emanuela Saracino and Ivano Lucarini of the National Research Council of Italy; and Jay Agrawal of VA Hudson Valley Health Care.