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.
MOLECULAR-DYNAMICS SIMULATIONS; DEMENTIA FENIB; ALZHEIMERS-DISEASE; FORMS POLYMERS; LUNG-DISEASE; NEUROSERPIN; PEPTIDES; SERPINOPATHIES; DEGRADATION; PROTEASOMES
Settore MED/04 - Patologia Generale
Settore FIS/03 - Fisica della Materia
11-apr-2014
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/238950
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