A comprehensive model for the diffusion and hybridization processes of
nucleic acid probes in fluorescence in situ hybridization
Abstract
Fluorescent in situ hybridization (FISH) has been extensively used in
the past decades for the detection and localization of nucleic acid
sequences or of the microorganisms themselves within samples. However, a
mechanistic approach of the whole FISH process is still missing, and the
main limiting steps for the hybridization to occur remain unclear. In
here, FISH is approached as a particular case of a diffusion-reaction
kinetics, where molecular probes move from the hybridization solution to
the target RNA site within the cells. Based on literature models, the
characteristic times taken by different molecular probes to diffuse
across multiple cellular barriers, and the reaction time associated with
the formation of the duplex molecular probe-RNA were estimated.
Structural and size differences at the membrane level of bacterial and
animal cells were considered. For bacterial cells, the limiting step for
diffusion is likely to be the peptidoglycan layer (characteristic time
of 2700-4524 s), whereas for animal cells the limiting step should be
the diffusion of the probe through the bulk (1.8-5.0 s) followed by the
diffusion through the lipid membrane (1 s). The information provided
here may serve as a basis to optimize FISH protocols.