Glycosaminoglycan-Mediated Selective Changes in the Aggregation States, Zeta Potentials, and Intrinsic Stability of Liposomes

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• 作者：Erin K. Nyren-Erickson ; Manas K. Haldar ; Jessica R. Totzauer ; Riley Ceglowski ; Dilipkumar S. Patel ; Daniel L. Friesner ; D. K. Srivastava ; Sanku Mallik
• 刊名：Langmuir
• 出版年：2012
• 出版时间：November 20, 2012
• 年：2012
• 卷：28
• 期：46
• 页码：16115-16125
• 全文大小：679K
• 年卷期：v.28,no.46(November 20, 2012)
• ISSN：1520-5827

文摘

Though the aggregation of glycosaminoglycans (GAGs) in the presence of liposomes and divalent cations has been previously reported, the effects of different GAG species and minor changes in GAG composition on the aggregates that are formed are yet unknown. If minor changes in GAG composition produce observable changes in the liposome aggregate diameter or zeta potential, such a phenomenon may be used to detect potentially dangerous oversulfated contaminants in heparin. We studied the mechanism of the interactions between heparin and its oversulfated glycosaminoglycan contaminants with liposomes. Herein, we demonstrate that Mg²⁺ acts to shield the incoming glycosaminoglycans from the negatively charged phosphate groups of the phospholipids and that changes in the aggregate diameter and zeta potential are a function of the glycosaminoglycan species and concentration as well as the liposome bilayer composition. These observations are supported by TEM studies. We have shown that the organizational states of the liposome bilayers are influenced by the presence of GAG and excess Mg²⁺, resulting in a stabilizing effect that increases the T_m value of DSPC liposomes; the magnitude of this effect is also dependent on the GAG species and concentration present. There is an inverse relationship between the percent change in aggregate diameter and the percent change in aggregate zeta potential as a function of GAG concentration in solution. Finally, we demonstrate that the diameter and zeta potential changes in POPC liposome aggregates in the presence of different oversulfated heparin contaminants at low concentrations allow for an accurate detection of oversulfated chondroitin sulfate at concentrations of as low as 1 mol %.