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Biophys J. 2013 Dec 3;105(11):2528-40. doi: 10.1016/j.bpj.2013.10.009.

Brownian dynamics of subunit addition-loss kinetics and thermodynamics in linear polymer self-assembly.

Author information

1
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota.

Abstract

The structure and free energy of multistranded linear polymer ends evolves as individual subunits are added and lost. Thus, the energetic state of the polymer end is not constant, as assembly theory has assumed. Here we utilize a Brownian dynamics approach to simulate the addition and loss of individual subunits at the polymer tip. Using the microtubule as a primary example, we examined how the structure of the polymer tip dictates the rate at which units are added to and lost from individual protofilaments. We find that freely diffusing subunits arrive less frequently to lagging protofilaments but bind more efficiently, such that there is no kinetic difference between leading and lagging protofilaments within a tapered tip. However, local structure at the nanoscale has up to an order-of-magnitude effect on the rate of addition. Thus, the kinetic on-rate constant, integrated across the microtubule tip (kon,MT), is an ensemble average of the varying individual protofilament on-rate constants (kon,PF). Our findings have implications for both catastrophe and rescue of the dynamic microtubule end, and provide a subnanoscale framework for understanding the mechanism of action of microtubule-associated proteins and microtubule-directed drugs. Although we utilize the specific example of the microtubule here, the findings are applicable to multistranded polymers generally.

PMID:
24314083
PMCID:
PMC3853320
DOI:
10.1016/j.bpj.2013.10.009
[Indexed for MEDLINE]
Free PMC Article

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