Health Australia (Commonwealth Union) – A team of biomedical engineers from the University of Sydney, working in collaboration with scientists from the University of Cambridge and Harvard University, has made significant strides in the development of advanced optical techniques for closely monitoring the formation of protein aggregates at the nanoscale.
Numerous diseases that impact the brain and nervous system are intricately linked to the process of protein aggregate formation, where liquid proteins transform into solid condensates within cells. However, this phenomenon remains shrouded in mystery, with little understood about its underlying mechanisms.
This transition from a liquid state to a solid state can set off the creation of amyloid fibrils, notorious for their role in forming plaques within neurons, a pivotal factor in neurodegenerative diseases like Alzheimer’s.
In their groundbreaking research, the biomedical engineers at the University of Sydney, in conjunction with their counterparts from the University of Cambridge and Harvard University, have harnessed sophisticated optical techniques to gain a close-range perspective on the intricate process governing the formation of these protein aggregates.
Their experiments involved scrutinizing a protein closely associated with Amyotrophic Lateral Sclerosis (ALS), the same disease that affected the renowned astrophysicist Professor Stephen Hawking. Through their meticulous observations, the Sydney engineers have been able to closely monitor the transformation of this protein as it transitions from a liquid state to a solid one.
Dr. Yi Shen, who is the the lead author of the research published in the Proceedings of the National Academy of Sciences (PNAS) in the United States, indicated that this represents a significant leap forward in the comprehension of the fundamental mechanisms underlying the development of neurodegenerative diseases.
Dr. Daniele Vigolo, a senior lecturer in the School of Biomedical Engineering and a member of the University of Sydney Nano Institute, further indicated that they can now directly witness the transformation of these crucial proteins from a liquid to solid state at the nanoscale, which is a scale of one millionth of a meter.
Proteins routinely undergo condensation during liquid-to-liquid phase separation, serving pivotal roles in numerous critical biological functions, including the formation of human embryos. This process facilitates biochemical reactions where precise protein concentrations are essential and fosters healthy protein-protein interactions.
However, as Dr. Shen, an ARC DECRA Fellow in the School of Chemical and Biomolecular Engineering and a member of Sydney Nano, pointed out, this process also elevates the risk of dysfunctional aggregation, leading to the formation of unhealthy solid protein aggregates within human cells.
“This can lead to aberrant structures associated with neurodegenerative diseases because the proteins no longer exhibit rapid reversibility back to liquid form. It is therefore crucial to monitor condensate dynamics, as they directly affect pathological states,” Dr. Shen added.
The groundbreaking nanoscale optical examination of this phenomenon, a world-first achievement, has enabled the research team to pinpoint that the shift from liquid to solid protein initiates at the interface of the protein condensates. This unique vantage point into the phase transition has also unveiled a surprising revelation: the internal structures of these protein conglomerates exhibit heterogeneity, a departure from the previous belief that they were uniform.
Dr. Vigolo emphasized, that their discoveries hold the potential to significantly enhance our fundamental understanding of neurodegenerative diseases.
“This means a promising new area of research to better understand how Alzheimer’s disease and ALS develops in the brain, affecting millions of people worldwide.”
Alzheimer’s disease is an ongoing and degenerative neurological condition that exerts its impact on memory, cognitive function, and behavior. A defining characteristic of Alzheimer’s disease is the buildup of amyloid plaques and tau protein tangles within the brain. These atypical protein accumulations disrupt the connections between nerve cells and ultimately result in the demise of brain cells.
