Fig. 3

Petri net representation of the reaction network that models an aggregation reaction. The monomer mass concentration (m), fibril mass concentration (M), fibril number concentration (P) and oligomer mass concentration (S), as well as the rate constants of their interconversions (see Table 2 for definitions), are indicated. M* represents monomer bound to fibril prior to its conversion or detachment, and P* represents a multistep elongation process including association and rearrangement. These processes fall into three categories: growth processes (elongation pathways), primary pathways, and secondary pathways (i.e. those that require the presence of fibrils). Note that no fibrillar mass is lost due to secondary nucleation or fragmentation, unless non-fibrillar oligomers are capable of detaching from fibril ends. Pathways shown in red and purple increase the relative fibrillar mass and number, respectively. In green are the pathways considered to be 'pro-oligomer,' meaning they lead to a net increase in the oligomer population. Conversely, pathways shown in blue represent microscopic processes that lead to oligomer dissociation. Adapted from Meisl et.al [185], to include the reactive flux towards and away from oligomers. Created with biorender.com