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

**Authors:** Stephani Stamboroski, Aparna Sai Malisetty, Kwasi Boateng, Jana Lierath, Jonas Aniol, Peter Schiffels, Paul-Ludwig Michael Noeske, Lucio Colombi Ciacchi, Susan Köppen, Dorothea Brüggemann

PMC · DOI: 10.1021/acs.biomac.5c01056 · 2025-09-05

## TL;DR

This study shows how different salts influence the formation of fibrinogen nanofibers during drying, offering insights for tissue engineering.

## Contribution

The paper introduces a two-dimensional Hofmeister series to explain salt-driven fibrillogenesis via ion pairing.

## Key findings

- KCl and NaCl produce smoother morphologies compared to Na-PO4 and K-PO4, which yield fibrous structures.
- Kosmotropic anions like sulfate promote fiber formation, while chaotropic anions like oxalate do not.
- Molecular dynamics simulations suggest ion-specific interactions at the fibrinogen/water interface.

## Abstract

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.

## Linked entities

- **Proteins:** FGB (fibrinogen beta chain)
- **Chemicals:** Na+ (PubChem CID 923), K+ (PubChem CID 813), KCl (PubChem CID 4873), NaCl (PubChem CID 5234), SO4^2– (PubChem CID 1117), oxalate (PubChem CID 71081), Mg^2+ (PubChem CID 888)

## Full-text entities

- **Genes:** FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}
- **Chemicals:** water (MESH:D014867), Salts (MESH:D012492), KCl (MESH:D011189), K+ (MESH:D011188), K-PO4 (-), oxygen (MESH:D010100), NaCl (MESH:D012965), Na+ (MESH:D012964)

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12522127/full.md

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Source: https://tomesphere.com/paper/PMC12522127