Mechanical Effects of Dynamic Binding between Tau Proteins on Microtubules during Axonal Injury.
Biophys J
; 109(11): 2328-37, 2015 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-26636944
ABSTRACT
The viscoelastic nature of axons plays a key role in their selective vulnerability to damage in traumatic brain injury (TBI). Experimental studies have shown that although axons can tolerate 100% strain under slow loading rates, even strain as small as 5% can rupture microtubules (MTs) during the fast loading velocities relevant to TBI. Here, we developed a computational model to examine rate-dependent behavior related to dynamic interactions between MTs and the MT-associated protein tau under varying strains and strain rates. In the model, inverted pairs of tau proteins can dynamically cross-link parallel MTs via the respective MT-binding domain of each tau. The model also incorporates realistic thermodynamic breaking and reformation of the bonds between the connected tau proteins as they respond to mechanical stretch. With simulated stretch of the axon, the model shows that despite the highly dynamic nature of binding and unbinding events, under fast loading rates relevant to TBI, large tensile forces can be transmitted to the MTs that can lead to mechanical rupture of the MT cylinder, in agreement with experimental observations and as inferred in human TBI. In contrast, at slow loading rates, the progressive breaking and reformation of the bonds between the tau proteins facilitate the extension of axons up to â¼100% strain without any microstructural damage. The model also predicts that under fast loading rates, individual MTs detach from MT bundles via sequential breaking of the tau-tau bonds. Finally, the model demonstrates that longer MTs are more susceptible to mechanical rupture, whereas short MTs are more prone to detachment from the MT bundle, leading to disintegration of the axonal MT ultrastructure. Notably, the predictions from the model are in excellent agreement with the findings of the recent in vitro mechanical testing of micropatterned neuronal cultures.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Axones
/
Proteínas tau
/
Fenómenos Mecánicos
/
Microtúbulos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biophys J
Año:
2015
Tipo del documento:
Article