Charge inversion accompanies DNA condensation by multivalent ions

The condensation of stiff, highly charged DNA molecules into compact structures by condensing agents ranging from multivalent ions 1 to small cationic proteins 2 , 3 is of major biological and therapeutic importance 4 , 5 , yet the underlying microscopic mechanism remains poorly understood 1 , 6 , 7 , 8 , 9 . It has been proposed 7 , 10 that DNA condensation is a purely electrostatic phenomenon driven by the existence of a strongly correlated liquid (SCL) of counterions at the DNA surface. The same theoretical argument predicts that multivalent counterions overcompensate the DNA charge when present at high concentration 11 , in turn destabilizing the condensates 12 . Here, we demonstrate the occurrence of DNA charge inversion by multivalent ions through measurements of the electrophoretic mobility of condensed DNA. By observing the multivalent-ion-induced condensation of a single DNA molecule using magnetic tweezers, we further show that charge inversion influences condensation by modulating the barrier for condensate nucleation in a manner consistent with the SCL mechanism.