A change in the mobility of membrane lipids affects the interaction of gramicidin s with human erythrocytes
Keywords:
erythrocytes, hemolysis, gramicidin S, temperature, activation energy, α- tocopherol, hydrogen peroxideAbstract
Gramicidin S interacts unspecifically with the lipid bilayer of the membrane of different cells and can disrupt the structure of not only erythrocyte membrane, but other blood cells as well and cause a change in their functional activity during the system application of the drug. The study of the interaction of membranotropic antimicrobial drugs with blood cell membranes makes it possible to explain the possible ways of increasing their therapeutic index. A change of the state of lipid bilayer affects GS interaction with membrane. Study of the interaction of gramicidin S with the cell membranes, modified by different physical and chemical factors, will make it possible to establish the mechanism of interaction in more detail and to determine the directions of the modification of the molecule of gramicidin S for the purpose of reduction in its hemolytic activity without loss of its antimicrobial effect. In the present paper with the help of the turbidimetry technique, the hemolysis of human erythrocytes under the action of gramicidin S in the presence of the different membrane modifiers was studied. It was shown that the character of the gramicidin binding to membranes depends on temperature - with an increase in the temperature from 22 to 40°С the concentration of gramicidin capable of causing the hemolysis of erythrocytes decreases. It was established that the decrease of the ordering of lipids in the erythrocyte membrane caused by lipid peroxidation in vitro facilitates the incorporation of gramicidin into the membrane, but, at the same time, it leads also to the decrease of the strength of gramicidin binding with the membranes. It was proven that the modification of the state of a membrane lipid bilayer with the peroxidation changes the hemolytic activity of gramicidin S. It was shown that there is a possibility of the directed modification of the membrane structure for increasing their resistance to the lytic action of gramicidin S.
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