Nucleated polymerisation in the presence of pre-formed seed filaments

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Abstract

We revisit the classical problem of nucleated polymerisation and derive a range of exact results describing polymerisation in systems intermediate between the well-known limiting cases of a reaction starting from purely soluble material and for a reaction where no new growth nuclei are formed. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

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  • Figure 1. Nucleated polymerisation in the presence of seed material. The thick dashed lines are the exact solution to the rate equations Equation (9); the thin solid lines are calculated from numerical simulations of the master equation Equation (1). The dotted lines are the initial gradients dM/dt|t=0 = M(0) + 2k+m(0)P (0)t; a lag-phase exists when the initial gradient is not the maximal gradient. The numbers accompanying each curve are k0/λ; Equation (14) predicts that a lag-phase only exists when this ratio is less than unity. (a): Nucleated polymerisation in the presence of an increasing quantity of seed material of a fixed average length (5000 monomers per seed) added at the beginning of the reaction. The seed concentrations given as a fraction of the total concentration of monomer present are right to left): 0, 0.01, 0.04, 0.1, 0.2, 0.5; (b): Nucleated polymerisation in the presence of a fixed quantity (1% of total monomer in the system) of seed material of varying average length. The average number of monomer per seed are (right to left): N/A (unseeded), 5000, 1000, 500, 200, 50. The other parameters for both panels are: mtot = 10 µM , nc = 3, knm nc−1
  • Table 1. Comparison of biofilament growth dominated by primary and secondary nucleation pathways. Primary nucleation processes create new aggregates at a rate that depends only on the concentration of monomeric peptide, whereas fragmentation creates new aggregates at a rate that depends only on the concentration of existing aggregates; monomer-dependent secondary nucleation creates new aggregates at a rate that depends on both the concentration of monomeric peptide and the concentration of existing aggregates. The dependencies of the latter two (secondary) nucleation processes on the existing aggregate concentration results in positive feedback: as the reaction proceeds, and proliferation through these mechanisms increases the concentration of aggregates, the rate at which these processes occur further is increased.

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APA

Cohen, S. I. A., Vendruscolo, M., Dobson, C. M., & Knowles, T. P. J. (2011). Nucleated polymerisation in the presence of pre-formed seed filaments. International Journal of Molecular Sciences, 12(9), 5844–5852. https://doi.org/10.3390/ijms12095844

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