Shear flow induced changes in apolipoprotein C-II conformation and amyloid fibril formation

Abstract

The misfolding and self-assembly of proteins into amyloid fibrils that occur in several debilitating diseases are affected by a variety of environmental factors, including mechanical factors associated with shear flow. We examined the effects of shear flow on amyloid fibril formation by human apolipoprotein C-II (apoC-II). Shear fields (150, 300, and 500 s-1) accelerated the rate of apoC-II fibril formation (1 mg/mL) approximately 5-10-fold. Fibrils produced at shear rates of 150 and 300 s-1 were similar to the twisted ribbon fibrils formed in the absence of shear, while at 500 s-1, tangled ropelike structures were observed. The mechanism of the shear-induced acceleration of amyloid fibril f..