Dynamics and Structures of Amyloid Aggregates under Fluid Flows

Area of Science:

• Biophysics
• Computational Biology
• Materials Science

Background:

• Amyloid-beta (Aβ) protein aggregation is implicated in neurodegenerative diseases.
• Understanding the influence of fluid dynamics on protein aggregation is crucial for disease modeling and therapeutic development.
• Previous studies have explored amyloid formation, but the specific impact of fluid flow on aggregation kinetics and aggregate mechanics remains less understood.

Purpose of the Study:

• To investigate the effect of fluid flow on the aggregation mechanisms of amyloid-beta (Aβ) proteins and peptides.
• To analyze the mechanical perturbation of (pre)fibrillar amyloid aggregates by different flow types (Couette and Poiseuille).
• To elucidate the transition in aggregation dynamics from diffusion-limited to advection-dominated regimes under shear stress.

Main Methods:

• Utilizing the OPEP (Oligomer Permeation and Equilibration) coarse-grained model for protein simulations.
• Employing the Lattice Boltzmann Molecular Dynamics (LBMD) technique to simulate fluid flows and their interactions with protein aggregates.
• Characterizing aggregate morphology and deformation under controlled shear rates and flow conditions.

Main Results:

• Amyloid aggregation rate significantly increases beyond a critical shear rate in Couette flow due to reduced aggregate collision times.
• A transition in aggregation dynamics from diffusion-limited to advection-dominated regimes was observed.
• Fluid flows were shown to mechanically deform (pre)fibrillar states, inducing pathological loop-like structures consistent with experimental observations.

Conclusions:

• Fluid flow dynamics play a critical role in accelerating amyloid-beta aggregation and influencing the structural outcomes.
• The findings provide insights into the formation of pathological amyloid structures under physiological flow conditions, such as in the brain's interstitial space.
• This research has potential implications for microfluidic applications and for understanding the pathogenesis of amyloid-related diseases.