An astrocyte displays natural star shape on new nanowire platform. Credit: Johns Hopkins University.
A new nanowire platform has captured the brain’s unsung heroes, astrocytes, for the first time in their natural habitat.
The scientists engineered a nanowire platform that mimics brain tissue to study astrocytes, the star-shaped cells critical for brain health.
Astrocytes are the brain’s most abundant and mysterious cells, responsible for regulating communication between neurons and helping to maintain the blood-brain barrier.
They are also highly dynamic shape-shifters, something they do not do on typical petri dishes, leaving major gaps in our understanding of how they operate.
Co-senior author Ishan Barman, a Johns Hopkins University bioengineer, said: “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?”
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.
An astrocyte loses its natural star-like form on glass. Credit: Johns Hopkins University.
Numerous diseases
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.
Barman said: “To truly understand astrocytes we need to replicate their environment. 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.
Co-senior author Annalisa Convertino of the National Research Council of Italy, said: “When grown on nanowire mats, astrocytes regain their star-like morphology, branching and maturing as they do in vivo in the brain.”
Capture
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.
Co-first author, Anoushka Gupta, a graduate student in Barman’s lab, said: “The ability to combine nanowire culture with high-resolution, label-free imaging was critical.
“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.
Barman said: “This is a major leap beyond flat culture models and paves the way for a new generation of ‘brain on a chip’ models.
“We believe this could herald the beginning of a new way to study neurogenerative diseases, drug effects and brain injuries.”
The study is published in Advanced Science.
