Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=41384068
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
The viscosity of protein and nucleic acid solutions and their folded structures
explored using the free-volume concept and Eyring s rate process theory
#MMPMID41384068
Hao T
RSC Adv
2025[Dec]; 15
(57
): 49374-49387
PMID41384068
show ga
This article aims to unify the understanding of protein and nucleic acid solution
viscosity by integrating the free-volume concept and Eyring's rate process
theory. The importance of controlling protein and nucleic acid solution viscosity
in therapeutic formulations and manufacturing cannot be overstated, as numerous
empirical and semi-empirical equations/models have been proposed to fit
experimental data in the literature. These models are intended to extrapolate
viscosity predictions at higher concentrations based on low-concentration data or
provide guidance on how to reduce viscosity by adjusting pH and adding salt.
However, none of these models can be universally applied to all systems,
providing reasonable interpretations of experimental results. We borrow the
reptation-tube concept from polymer science to treat the molecules of proteins
and nucleic acids, and introduce the aspect ratio parameter to describe the
fibrousness of the molecular shapes of the proteins and nucleic acids. The
obtained equations can adequately correlate the viscosity with protein and
nucleic acid volume fraction, salt concentration, zeta potential, pH, and
temperature, and fit many experimental data very well. They show that the
viscosity increases almost linearly with the volume fraction in
low-volume-fraction regions, but increases dramatically with the volume fraction
in high-volume-fraction regions; increases gradually with both zeta potential and
the aspect ratio of the molecular chains; decreases with the square root of the
ionic strength; reaches a minimum point with pH; and generally decreases with
temperature, except in DNA solutions due to the transition from double-stranded
to single-stranded molecules, etc. The viscosity of several protein and DNA
solutions are regressed with our equations and very good agreements are obtained.
Our work deepens the physical understanding of critical parameters, and provides
clues for lowering viscosity in pharmaceutical formulations.
free
free
free
