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A two-step reversible-irreversible model can account for a negative activation energy in an Arrhenius plot
J L Muench1, J Kruuv, J R Lepock
1Department of Physics, University of Waterloo, Ontario, Canada.
Cryobiology
|April 1, 1996
Summary
Low temperatures can kill cells through a two-step process, involving an initial reversible change followed by an irreversible event. This explains apparent negative activation energies observed in hypothermic cell inactivation studies.
Area of Science:
- Cellular biology
- Biophysics
- Cryobiology
Background:
- Cellular inactivation at low temperatures exhibits unusual kinetics.
- Arrhenius plots show apparent negative activation energies in some hypothermic studies.
- Understanding these mechanisms is crucial for cryopreservation and understanding cold injury.
Purpose of the Study:
- To explain the phenomenon of apparent negative activation energies in hypothermic cell killing.
- To propose a mechanistic model for cold-induced cellular inactivation.
- To identify potential molecular events underlying hypothermic cell death.
Main Methods:
- Analysis of Arrhenius plots for mammalian cells and Drosophila embryos.
- Theoretical modeling of a two-step reaction mechanism (reversible followed by irreversible).
- Comparison of the model with proposed biological events.
Main Results:
- Observed "apparent negative" activation energies at low temperatures were explained by a two-step process.
- The model successfully accounts for the kinetic data.
- Two plausible mechanisms involving membrane transitions or protein denaturation were identified.
Conclusions:
- Hypothermic cell killing is likely mediated by a two-step process with a reversible first step and an irreversible second step.
- Membrane lipid phase transitions or protein cold denaturation followed by aggregation are potential mechanisms.
- This model provides a framework for understanding cold injury and optimizing cryopreservation techniques.