Single-molecule studies reveal that the Ca2+ ions form maximum bridges with polyacrylic acid at physiological concentration of the cation

The interaction between poly(acrylic acid) (PAA) and Ca 2+ is central to biological and ion-responsive materials, yet how the coordination behavior varies with Ca 2+ concentration remains insufficiently understood. Here, single-molecule force spectroscopy was used to probe the mechanical response of individual PAA chains in CaCl 2 solutions from 10 –6 to 1 M. Taking the backbone-determined inherent elasticity of PAA, together with its single-chain mechanics in water as references, a pronounced bell-shaped dependence of energy dissipated on Ca 2+ concentration was identified, with a maximum near 10 –3 M. This nonmonotonic trend originates from a concentration-regulated transition in binding modes: dual-carboxylate bridging dominates at low Ca 2+ concentrations (≤ 10 –3 M), enhancing energy dissipation upon rupture, whereas mono-carboxylate binding prevails at higher concentrations (> 10 –3 M), resulting in reduced dissipation. These results reveal a concentration-regulated dual-to-mono coordination switch governing PAA-Ca 2+ interactions, with calcium-bridge formation maximized at physiological Ca 2+ levels, providing molecular insight for designing PAA-Ca 2+ -based materials.