Cooperativity in classical biophysics originates from molecular interactions; nonlinear feedbacks in biochemical networks regulate dynamics inside cells. Using stochastic reaction kinetic theory, we discuss cooperative transitions in cellular biochemical processes at both the macromolecular and the cellular levels. We show that fluctuation-enhanced sensitivity (stochastic focusing) shares an essential feature with the transition in a bistable system. The same theory explains zeroth-order ultrasensitivity with temporal cooperativity. Dynamic cooperativity in fluctuating enzyme (i.e., dynamic disorder), stochastic focusing, and the recently proposed stochastic binary decision all have a shared mechanism: They are generalizations of the hyperbolic response of Michaelis-Menten kinetics /(+), with fluctuating or stochastic . Sigmoidal dependence on substrate concentration necessarily yields affinity amplification for competing ligands; both sigmoidal response and affinity amplification exhibit a square law. We suggest two important characteristics in a noise: its multimodal distribution structure and its temporal irreversibility. The former gives rise to self-organized complexity, and the latter contains useful, albeit hidden, free energy that can be utilized for biological functions. There could be structures and energy in biochemical fluctuations.


Article metrics loading...

Loading full text...

Full text loading...


Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error