Fluorescence Correlation Spectroscopy and Nonlinear Stochastic Reaction-Diffusion

TL;DR

This paper investigates the limitations of traditional linear fluctuation theory in fluorescence correlation spectroscopy (FCS) for nonlinear reaction-diffusion systems, especially in small biological environments, using simulations to explore deviations.

Contribution

It extends the stochastic reaction theory to nonlinear reaction-diffusion systems, providing a framework for analyzing FCS in complex biological contexts.

Findings

Deviations from linear FCS are small for simple reactions with many molecules.

Significant deviations occur when molecule numbers are small and reactions are nonlinear.

Current linear FCS theory remains adequate for many biological measurements.

Abstract

The currently existing theory of fluorescence correlation spectroscopy(FCS) is based on the linear fluctuation theory originally developed by Einstein, Onsager, Lax, and others as a phenomenological approach to equilibrium fluctuations in bulk solutions. For mesoscopic reaction-diffusion systems with nonlinear chemical reactions among a small number of molecules, a situation often encountered in single-cell biochemistry, it is expected that FCS time correlation functions of a reaction-diffusion system can deviate from the classic results of Elson and Magde. We first discuss this nonlinear effect for reaction systems without diffusion. For nonlinear stochastic reaction-diffusion systems here are no closed solutions; therefore, stochastic Monte-Carlo simulations are carried out. We show that the deviation is small for a simple bimolecular reaction; the most significant deviations occur when the number of molecules is small and of the same order. Our results show that current linear FCS theory could be adequate for measurements on biological systems that contain many other sources of uncertainties. At the same time it provides a framework for future measurements of nonlinear, fluctuating chemical reactions with high-precision FCS. Extending Delbr\"uck-Gillespie's theory for stochastic nonlinear reactions with rapidly stirring to reaction-diffusion systems provides a mesoscopic model for chemical and biochemical reactions at nanometric and mesoscopic level such as a single biological cell.