Hofmeister-Driven Ion Pairing in Monovalent Salts Directs Fibrinogen Nanofiber Assembly during Drying

Fibrinogen nanofiber scaffolds hold promise for tissue engineering and wound healing due to their similarity to fibrin clots. We studied how alkaline salts (Na⁺, K⁺) influence fibrinogen precipitation during drying of highly saline dispersions. In situ roughness (Aq) monitoring revealed coprecipitation of salts and fibrinogen. SEM and Aq mapping showed morphologies from smooth (KCl) and faintly fibrous (NaCl) to highly rough and finely fibrous (Na-PO₄, K-PO₄). FTIR indicated that secondary structure changes are not always linked to fiber formation. XPS showed a stronger Na⁺ uptake, especially with fiber-forming salts. With Na⁺ and oxygen-containing polyvalent anions, kosmotropic SO₄^2- induced fibers, while chaotropic oxalate yielded smooth films. Mg²⁺ or K⁺ with SO₄^2- did not form any fibers. Molecular dynamics simulations suggest ion-specific binding at the fibrinogen/water interface. We propose a two-dimensional Hofmeister series for tailoring fibrillogenesis via kosmotropic anion-cation pairs, concluding that fiber assembly is salt-driven and governed by cooperative kosmotropic effects.