Counterion Condensation on Heparin Oligomers

• Published in: Biomacromolecules Vol. 14; no. 4; pp. 1113 - 1121
• Main Authors: Minsky, Burcu Baykal, Atmuri, Anand, Kaltashov, Igor A, Dubin, Paul L
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 08.04.2013
• Subjects: Applied sciences; Biological and medical sciences; Electrolytes - chemistry; Electrophoresis, Capillary; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Heparin - chemistry; Heparitin Sulfate - chemistry; In solution. Condensed state. Thin layers; Mass Spectrometry; Molecular biophysics; Natural polymers; Physico-chemical properties of biomolecules; Physicochemistry of polymers; Starch and polysaccharides; Monodispersed polymer; Capillary electrophoresis; Electrophoretic mobility; Oside polymer; Low molecular weight heparin; Aqueous solution; Experimental study; Oligomer; Dimension spectrum
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm400006g

The electropherogram of native heparin shows a broad distribution of mobilities μ, which truncates abruptly at a notably high μ = 4.7 × 10–4 cm2 V–1 s–1. This highly skewed mobility distribution is also found for the 20-saccharide chain, which shows from mass spectrometry a more uniform (symmetrical) with respect to sulfation level. Since a partially degraded heparin exhibits oligomer peaks with μ> 5 × 10–4 cm2 V–1 s–1 (appearing to escape the limitation of the mobility value for native heparin), we examined the electrophoretic behavior of chain-length monodisperse heparin oligomers. Their mobilities varied inversely with the logarithm of the contour length, L, for L from 3 to 10 nm and reached an asymptotic limit for L > 20 nm. The generality of this effect was indicated by similar behavior for oligomers of poly(styrene sulfonate). A recent theory of polyelectrolyte end effects (Manning, G. S. Macromolecules 2008, 41, 6217–6227), in which chain termini exhibit reduced counterion condensation was found to quantitatively account for these results. A qualitative explanation for the anomalously high value of μ of native heparin, 10–20% higher than those seen for synthetic polyelectrolytes of higher linear charge density, is suggested on the basis of similar junction effects (Manning, G. S. Macromolecules 2008, 41, 6217–6227), which reduce counterion condensation at the interfaces of regions of high and low sulfation. We suggest that these effects should be considered in models for the biofunctionality of the regulated high and low sulfation (NS/NA) domains of heparan sulfate.