The factor that tips you over the edge from being at risk for a disease to actually developing the disease is not always clear. Now, researchers from Japan report one factor that triggers problematic proteins to start behaving badly.
In a study published recently in npj biosensing, researchers from Osaka University have revealed that high liquid flow rates could cause aggregation-prone proteins to start sticking together.
Amyloidosis is the basis of several serious diseases, such as Alzheimer disease and Parkinson disease. This process involves the formation of amyloid fibrils, crystal-like collections of misfolded proteins that clump together when the proteins are highly concentrated (supersaturated) in liquids like blood or cerebrospinal fluid.
“Amyloidosis is a serious concern in our aging society, as elderly individuals are more likely to develop these conditions,” says lead author of the study Yuji Goto. “Although studies have shown that supersaturation is a necessary condition for amyloid fibril formation, the factors that actually induce protein aggregation in supersaturated fluids remain unclear.”
To address this, the researchers ran a model amyloid-forming protein, hen egg white lysozyme, through a peristaltic pump similar to those used for dialysis. They then used fluorescence detection to monitor hen egg white lysozyme amyloid formation as it was propelled through the pump system.
“The results were highly intriguing,” explains Hirotsugu Ogi, senior author. “Flow through the peristaltic pump system effectively triggered amyloid formation by hen egg white lysozyme.”
Next, the researchers tested amyloid-forming proteins associated with human disease, including a-synuclein, amyloid b 1-40, and b2-microglobulin, and found that they also formed amyloids in the peristaltic pump system. Their calculations showed that the shear stress on the liquid caused by the pumping motion mechanically broke supersaturation to induce amyloid formation.
“Our findings suggest that shear flow forces in various fluids in our body, such as blood and cerebrospinal fluid, could trigger amyloid formation,” says Goto.
Given that some medical procedures like dialysis use peristaltic pumps, it is possible that this could be another trigger of amyloidosis. Understanding the effects of shear forces on protein supersaturation could clarify how amyloid aggregates begin to form nucleation and help develop treatment strategies.