A mathematical model of plasmin-mediated fibrinolysis of single fibrin fibers
Fig 2
A: There are 11 reactions considered in the model: 5 involving unbinding, degradation, or exposure (non-crawling reactions), and 6 crawling reactions (4 within the same protofibril and 2 to a neighboring protofibril). N is a cryptic doublet, N00 is an exposed doublet with nothing bound, N03 is an exposed doublet with a plasmin bound, ϕ00 is a degraded doublet with nothing bound, and ϕ03 is a degraded doublet with a plasmin bound. Solid black arrows indicate an unbinding reaction, dashed arrows indicate a degradation or exposure reaction, and red arrows indicate a crawling reaction. Reactions are labeled as ‘Ri’ with i = 1, …, 11. The unbinding reactions are R1 (plasmin unbinds from N03 resulting in N00) and R4 (plasmin unbinds from ϕ03 resulting in ϕ00). The exposure reaction is R5 (cryptic doublet N is exposed by plasmin to create N00). The degradation reactions are R2 (plasmin degrades N00, turning it into ϕ00) and R3 (plasmin degrades N03, turning it into ϕ03). There are 4 possible crawling reactions within the same protofibril: R6 (plasmin crawls from N03 to ϕ00, resulting in N00 and ϕ03), R7 (plasmin crawls from ϕ03 to N00, resulting in ϕ00 and N03), R8 (plasmin crawls from N03 to N00, resulting in N00 and N03), and R9 (plasmin crawls from ϕ03 to ϕ00 resulting in ϕ00 and ϕ03). Note that R8 and R9 do not change the state of the system, but do take time to occur, so we include them in the Gillespie algorithm. Finally, there are 2 possible crawling reactions from the given protofibril to a neighboring protofibril: R10 (plasmin crawls from N03 at this protofibril to a randomly chosen exposed doublet on a neighboring protofibril) and R11 (plasmin crawls from ϕ03 at this protofibril to a randomly chosen exposed doublet on a neighboring protofibril). B: The degradation reaction results in loss of doublets (degraded doublets represented by a red X in the leftmost figure). If some but not all of the doublets (protofibril chains) are degraded, then that protofibril is considered to be partially degraded (blue X). If all 6 doublets are degraded, then that protofibril is considered to be fully degraded (red X in middle figure cross-section). At a given fraction of degraded doublets, say 2/3, there will be a mix of undegraded, partially degraded, and fully degraded protofibrils (rightmost figure).