Figure 1.

Schematic Illustration of Fibril Division in the Amyloid Life Cycle

(A) The life cycle of amyloid assembly where soluble monomeric proteins (circles) are converted into the amyloid state with a cross-β conformation (the parallelograms). The colored arrows represent the four main processes in amyloid assembly. Red arrows represent primary nucleation, which may occur as homogeneous nucleation in solution and heterogeneous nucleation at interfaces. Primary nucleation may also occur subsequent to liquid-liquid phase separation or phase transitions (Khan et al., 2018). Purple arrows represent secondary nucleation, which may occur as heterogeneous nucleation at surfaces presented by preformed aggregates. Blue arrows represent growth by elongation at fibril ends. Yellow arrows and box represent fibril division (e.g., fibril fragmentation or breakage). The arrows may represent consecutive reversible steps, and the thickness of the arrows symbolizes the relative rates involved in the processes.

(B) A simple model of fibril division, where a given parent fibril particle of length y divides to give rise to two daughter fibril particles of size x and y-x. The model does not otherwise identify the lineage of the individual fibrils.

(C) The division model assumes that each parent fibril particle divides into exactly two daughter particles at each microscopic reaction step.

(D) The division model assumes that the division rate for each microscopic step is identical as long as the resulting two particles have the same size.