Several neurological disorders are associated with the aggregation of aberrant proteins, often localized in intracellular organelles such as the endoplasmic reticulum. Here we study protein aggregation kinetics by mean-field reactions and three dimensional Monte carlo simulations of diffusion-limited aggregation of linear polymers in a confined space, representing the endoplasmic reticulum. By tuning the rates of protein production and degradation, we show that the system undergoes a non-equilibrium phase transition from a physiological phase with little or no polymer accumulation to a pathological phase characterized by persistent polymerization. A combination of external factors accumulating during the lifetime of a patient can thus slightly modify the phase transition control parameters, tipping the balance from a long symptomless lag phase to an accelerated pathological development. The model can be successfully used to interpret experimental data on amyloid-Î 2 clearance from the central nervous system.
Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase transition / Z. Budrikis, G. Costantini, C.A.M. La Porta, S. Zapperi. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 5(2014 Apr 11), pp. 3620.1-3620.8. [10.1038/ncomms4620]
Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase transition
C.A.M. La Porta;S. Zapperi
2014
Abstract
Several neurological disorders are associated with the aggregation of aberrant proteins, often localized in intracellular organelles such as the endoplasmic reticulum. Here we study protein aggregation kinetics by mean-field reactions and three dimensional Monte carlo simulations of diffusion-limited aggregation of linear polymers in a confined space, representing the endoplasmic reticulum. By tuning the rates of protein production and degradation, we show that the system undergoes a non-equilibrium phase transition from a physiological phase with little or no polymer accumulation to a pathological phase characterized by persistent polymerization. A combination of external factors accumulating during the lifetime of a patient can thus slightly modify the phase transition control parameters, tipping the balance from a long symptomless lag phase to an accelerated pathological development. The model can be successfully used to interpret experimental data on amyloid-Î 2 clearance from the central nervous system.File | Dimensione | Formato | |
---|---|---|---|
ncomms4620.pdf
accesso aperto
Tipologia:
Publisher's version/PDF
Dimensione
803.54 kB
Formato
Adobe PDF
|
803.54 kB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.