A universal description for the experimental behavior of salt-(in)dependent oligocation-induced DNA condensation

Abstract

We report a systematic study of the condensation of plasmid DNA by oligocations with variation of the charge, Z, from +3 to +31. The oligocations include a series of synthetic linear epsilon-oligo(l-lysines), (denoted epsilon Kn, n = 3-10, 31; n is the number of lysines with the ligand charge Z = n+1) and branched alpha-substituted homologues of epsilon K10: epsilon YK10, epsilon LK10 (Z = +11); epsilon RK10, epsilon YRK10 and epsilon LYRK10 (Z = +21). Data were obtained by light scattering, UV absorption monitored precipitation assay and isothermal titration calorimetry in a wide range concentrations of DNA and monovalent salt (KCl, C-KCl). The dependence of EC50 (ligand concentration at the midpoint of DNA condensation) on C-KCl shows the existence of a salt-independent regime at low C-KCl and a salt-dependent regime with a steep rise of EC50 with increase of C-KCl. Increase of the ligand charge shifts the transition from the salt-independent to salt-dependent regime to higher C-KCl. A novel and simple relationship describing the EC50 dependence on DNA concentration, charge of the ligand and the salt-dependent dissociation constant of the ligand-DNA complex is derived. For the epsilon-oligolysines epsilon K6-epsilon K10, the experimental dependencies of EC50 on C-KCl and Z are well-described by an equation with a common set of parameters. Implications from our findings for understanding DNA condensation in chromatin are discussed.