A Kinetic Model for Cell Damage Caused by Oligomer Formation

Biophys J. 2015 Oct 6;109(7):1338-46. doi: 10.1016/j.bpj.2015.08.007.

Abstract

It is well known that the formation of amyloid fiber may cause invertible damage to cells, although the underlying mechanism has not been fully understood. In this article, a microscopic model considering the detailed processes of amyloid formation and cell damage is constructed based on four simple assumptions, one of which is that cell damage is raised by oligomers rather than mature fibrils. By taking the maximum entropy principle, this microscopic model in the form of infinite mass-action equations together with two reaction-convection partial differential equations (PDEs) has been greatly coarse-grained into a macroscopic system consisting of only five ordinary differential equations (ODEs). With this simple model, the effects of primary nucleation, elongation, fragmentation, and protein and seeds concentration on amyloid formation and cell damage have been extensively explored and compared with experiments. We hope that our results will provide new insights into the quantitative linkage between amyloid formation and cell damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / metabolism
  • Cell Physiological Phenomena / physiology*
  • Computer Simulation
  • Ions / metabolism
  • Kinetics
  • Models, Biological*
  • Protein Multimerization*

Substances

  • Amyloid
  • Ions