Speaker
Description
Amyloid-β (Aβ) aggregation provides a prototypical example of geometry-regulated self-assembly in biological systems. While amyloid growth is often described in terms of chemical kinetics or tip-growth models, how single-molecule diffusion on fibril surfaces is shaped by physical constraints remains incompletely understood. Here, we use coarse-grained molecular dynamics simulations to investigate the surface-mediated diffusion of Aβ42 monomers on preformed fibrils. We find that monomer mobility is highly anisotropic: monomers aligned parallel to the fibril axis diffuse significantly faster than those in perpendicular orientations. This orientation dependence is further modulated by surface roughness, with smoother regions supporting enhanced mobility. At the microscopic level, monomer motion is governed by a periodic energy landscape arising from the intrinsic surface topography of the fibril and the finite size of the monomer. This coupling between geometry and contact patterns produces a biased random-walk dynamics, linking local interfacial structure to effective transport along the fibril. Moreover, fibril twisting introduces a regulatory geometric niche that selectively stabilizes specific orientations, tuning diffusion rates to biologically relevant timescales. Together, these results connect single-molecule diffusion, surface geometry, and collective fibril growth, leading to a refined kinetic picture that extends beyond classical tip-growth models. More broadly, this work illustrates how directional energy landscapes and molecular orientation act as physical control parameters in amyloid assembly, offering a general framework for understanding surface-guided self-organization across biological scales.
