Membrane Disintegration Caused by the Steroid Saponin Digitonin Is Related to the Presence of Cholesterol

Molecules

Ikhwan Resmala Sudji¹  Yamunadevi Subburaj³  Nataliya Frenkel²  Ana J. García-Sáez³  Michael Wink¹ 

[1] Department of Biology, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, INF 364, 69120 Heidelberg, Germany;Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, 69120 Heidelberg, Germany;Interfaculty Institute for Biochemistry, University of Tübingen, 72076 Tübingen, Germany;

关键词: digitonin;    cholesterol;    calcein release;    giant unilamellar vesicles;    dynamic light scattering;    membrane permeability;   

DOI  :  10.3390/molecules201119682

来源: mdpi

【 摘 要 】

In the present investigation we studied the molecular mechanisms of the monodesmosidic saponin digitonin on natural and artificial membranes. We measured the hemolytic activity of digitonin on red blood cells (RBCs). Also different lipid membrane models (large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs) in the presence and absence of cholesterol were employed. The stability and permeability of the different vesicle systems were studied by using calcein release assay, GUVs membrane permeability assay using confocal microscopy (CM) and fluorescence correlation spectroscopy (FCS) and vesicle size measurement by dynamic light scattering (DLS). The results support the essential role of cholesterol in explaining how digitonin can disintegrate biological and artificial membranes. Digitonin induces membrane permeability or causes membrane rupturing only in the presence of cholesterol in an all-or-none mechanism. This effect depends on the concentrations of both digitonin and cholesterol. At low concentrations, digitonin induces membrane permeability while keeping the membrane intact. When digitonin is combined with other drugs, a synergistic potentiation can be observed because it facilitates their uptake.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.