Ion jacket regulates flexible biopolymer conformation in salt mixtures

Polysaccharides, proteins, and single-stranded nucleic acids are biologically important flexible polyelectrolytes (PEs). Due to their charge and flexibility, their conformations are usually very sensitive to ionic strength. Prior work has characterized how PE stiffness scales with 1:1 salt, but biological solutions contain multiple ion species and valences. In those cases, PEs are affected by an interplay of strong electrostatics (leading to multivalent ion condensation) and weaker long-range screening, but it is not known how this will manifest in the chain stiffness. We use single-molecule magnetic tweezers to measure three biological PEs in various salt mixtures. We observe a surprising regime in which a small amount of multivalent salt eliminates the effect of ionic strength. Simulations reveal an “ion jacket” layer of condensed multivalent cations and loosely associated monovalent ions, in which an ion exchange process protects against changes in bulk ionic strength. A model that relies on local Donnan equilibrium rather than Debye screening predicts salt-dependent ion condensation that accounts for the insensitivity. This unexpected regime where charge-renormalized chains ignore ionic strength has implications for both in vivo biopolymer structure and biomaterials design.