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

Abstract

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.

Structural, kinetic, and thermodynamic aspects of insulin aggregation

“…Moreover, another modified form of the three-parameter sigmoidal function of eqn (22) was also used to fit the time-course monomer extinction curve for the shear-induced aggregation of insulin. 100–102 where C 0 = the initial monomer concentration, C i = the initial soluble monomer concentration, t 1/2 = the time required to reduce the protein concentration by half, and k = the intrinsic rate coefficient, which depends on nucleation and fibril elongation.…”

“…3 Moreover, another modified form of the three-parameter sigmoidal function of eqn (22) was also used to fit the timecourse monomer extinction curve for the shear-induced aggregation of insulin. [100][101][102] rate coefficient, which depends on nucleation and fibril elongation. Apart from the above parameters, the authors also considered four additional matrices to assess the fibrillization time scale.…”

Advances in Microgravity Directed Tissue Engineering

“…[19,125] And also, the convenience of sample transportation and recovery is very limited in ISS. [8,126] The relevant flight opportunities are rare and costly, and the tissue engineering may not always be the priority. [8,[127][128][129] Therefore, the ground-based microgravity simulator is more feasible to obtain the microgravity environment.…”

Finite-time adaptive control for microgravity vibration isolation system with full-state constraints

“…Because of its potential to provide a quiescent environment. For instance, space optical telescopes need high pointing accuracy mechanical systems [1][2][3], and the microgravity missions including space gravitational wave detection [4], microgravity biology and chemistry studies [5] need an ultra-stable platform. However, the microvibration can affect the operation of optical equipment and other acceleration-sensitive scientific equipment, which leads to a renewed interest in space vibration suppression [6][7][8].…”