Fluctuations, correlations and the estimation of concentrations inside cells

PEREZ IPIÑA EMILIANO; PONCE DAWSON SILVINA

Seminario; Proteomics-BioMaPS & CABM Seminar Progam; 2015

The transmission of information inside cells usually involves changesin the concentration of signaling molecules that need to be read byother target molecules. This occurs in a highly fluctuatingenvironment, but, yet cells respond quite reliably to various changesshowing that they read concentration variations with great accuracy.Concentration estimates can always be improved by averaging over time,but this time could be exceedingly long in the case of very lowconcentrations.  Low concentrations and fluctuations also affect theability of experimenters to quantitate the  processes at work insidecells. Fluctuations, however, are exploited by various opticaltechniques ({\it e.g.}, Fluorescence or Image CorrelationSpectroscopy, FCS or ICS) to estimate transport rates andconcentrations from the analysis of fluorescence fluctuations. Theseestimates use an underlying model that makes judicious assumptions onthe behavior of particle numbers most often assuming that they obeyPoisson statistics.  We found that the interaction of signalingmolecules with immobile species introduces correlations thatinvalidate this assumption affecting directly the relationship betweenthe weigth of the fluorescence autocorrelation function obtained fromexperiments and the molecules concentration. We also found that, formoving binding sites, there is a fundamental limit to the accuracywith which the weight can be determined that depends on the averagingand correlation times but not on the number of particles in theobservation volume. The limited volume over which the moleculesmovement takes place introduces another type of correlation that canimprove the accuracy with which the weight and thus, theconcentration, can be determined provided that one uses the correctunderlying model.