The incorrect folding and aggregation of proteins plays an important role in a range of destructive disorders, including neurodegenerative diseases like Alzheimer's and Parkinson's. However, the physics underlying protein misfolding and aggregation is scarcely understood and is therefore still one of the most important challenges of modern-day biophysics.
Researchers from this programme aim to unravel the physics mechanisms underlying the dynamics, and especially the initial stages, of protein aggregation. This programme specifically focuses on the mechanisms that play a role in the aggregation of the human protein alpha-synuclein, which is involved in Parkinson's disease.
A closer look
One of the key research questions is: 'How do protein aggregations disrupt the integrity of cell membranes?' FOM PhD researcher Aditya Iyer has taken a closer look at this process by forming lipid membranes about five nanometres thick on glass (so-called supported lipid bilayers). He followed the effect of the protein alpha-synuclein on these membranes using optical microscopy. The researchers stained the proteins and lipids with a fluorescent dye to follow them as accurately as possible.
In a mixture that consists for fifty percent of negatively charged and fifty percent of uncharged lipids, the protein was found to aggregate on the membrane after 18 hours. After 42 hours the protein aggregates were bigger and there were indications for tears and holes in the membrane. Microscopy images revealed that after 42 hours, aggregates consisted of both proteins and lipids – it appears that the aggregation of protein sucks lipids out the membrane as result of which the membrane becomes damaged.