Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase transition.
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-β clearance from the central nervous system.
Institute for Scientific Interchange Foundation, Via Alassio 11/C, Torino 10126, Italy.
Zoe
Z
Budrikis
Istituto per l'Energetica e le Interfasi, CNR-Consiglio Nazionale delle Ricerche, Via R. Cozzi 53, Milano 20125, Italy.
Giulio
G
Costantini
Department of Biosciences, University of Milano, via Celoria 26, Milano 20133, Italy.
Caterina A M
CA
La Porta
1] Institute for Scientific Interchange Foundation, Via Alassio 11/C, Torino 10126, Italy [2] Istituto per l'Energetica e le Interfasi, CNR-Consiglio Nazionale delle Ricerche, Via R. Cozzi 53, Milano 20125, Italy.
Stefano
S
Zapperi
D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007700:Kinetics; D009010:Monte Carlo Method; D044367:Phase Transition; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D011506:Proteins