Title: Hydrodynamic models for the diffusivity of type A botulinum neurotoxin

Authors: Frank J. Lebeda, Michael Adler

Addresses: Integrated Toxicology Division, US Army Medical Research Institute of Infectious Diseases, Ft. Detrick, MD 21702-5012, USA; Combat Casualty Care Research Program, 504 Scott Street, Ft. Detrick, MD 21702-5012, USA. ' Neurobehavioral Toxicology Branch, Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, USA

Abstract: The times-to-maximum effect of type A botulinum neurotoxin (BoNT/A) depend to some extent on biophysical and biochemical variables. These times range from <3 h (isolated nerve-muscle preparations) to 1-3 weeks (healthy human volunteers). Hydrodynamic equations were solved for different models, some of which produced values of the diffusion coefficient (D) that are comparable to those of other proteins. Other results differed by up to five orders of magnitude. Because the in vivo findings were not related to an unusually small value for D, we propose that there is a protective reservoir for BoNT/A in vivo and possibly for other serotypes.

Keywords: diffusion coefficient; latency; onset; delay; radius of gyration; radius of hydration; time-to-peak; velocity; viscosity; botulinum neurotoxin; BoNT/A; botulism; BoNT; modelling; biophysical variables; biochemical variables; hydrodynamic equations; proteins.

DOI: 10.1504/TBJ.2010.039114

The Botulinum Journal, 2010 Vol.1 No.4, pp.393 - 406

Published online: 17 Mar 2011 *

Full-text access for editors Full-text access for subscribers Purchase this article Comment on this article