Force spectroscopy unravels the role of ionic strength on DNA-cisplatin interaction: Modulating the binding parameters

Abstract

In the present work we have gone a step forward in the understanding of the DNA-cisplatin interaction, investigating the role of the ionic strength on the complexes formation. To achieve this task, we use optical tweezers to perform force spectroscopy on the DNA-cisplatin complexes, determining their mechanical parameters as a function of the drug concentration in the sample for three different buffers. From such measurements, we determine the binding parameters and study their behavior as a function of the ionic strength. The equilibrium binding constant decreases with the counterion concentration ([Na]) and can be used to estimate the effective net charge of cisplatin in solution. The cooperativity degree of the binding reaction, on the other hand, increases with the ionic strength, as a result of the different conformational changes induced by the drug on the double-helix when binding under different buffer conditions. Such results can be used to modulate the drug binding to DNA, by appropriately setting the ionic strength of the surrounding buffer. The conclusions drawn provide significant new insights on the complex cooperative interactions between the DNA molecule and the class of platinum-based compounds, much used in chemotherapies.