Amyloidogenesis via interfacial shear in a containerless biochemical reactor aboard the International Space Station.

Fluid interfaces significantly influence the dynamics of protein solutions, effects that can be isolated by performing experiments in microgravity, greatly reducing the amount of solid boundaries present, allowing air-liquid interfaces to become dominant. This investigation examined the effects of protein concentration on interfacial shear-induced fibrillization of insulin in microgravity within a containerless biochemical reactor, the ring-sheared drop (RSD), aboard the international space station (ISS). Human insulin was used as a model amyloidogenic protein for studying protein kinetics with applications to in situ pharmaceutical production, tissue engineering, and diseases such as Alzheimer's, Parkinson's, infectious prions, and type 2 diabetes. Experiments investigated three main stages of amyloidogenesis: nucleation studied by seeding native solutions with fibril aggregates, fibrillization quantified using intrinsic fibrillization rate after fitting measured solution intensity to a sigmoidal function, and gelation observed by detection of solidification fronts. Results demonstrated that in surface-dominated amyloidogenic protein solutions: seeding with fibrils induces fibrillization of native protein, intrinsic fibrillization rate is independent of concentration, and that there is a minimum fibril concentration for gelation with gelation rate and rapidity of onset increasing monotonically with increasing protein concentration. These findings matched well with results of previous studies within ground-based analogs.