Charge regulation in peptide self-assembly and hydrogelation
Gentile, Luigi LU ; Frohm, Birgitta LU ; Malmendal, Anders LU ; Åkerfeldt, Karin S. LU ; Olsson, Ulf LU
and Linse, Sara
LU
(2025)
In Journal of Colloid and Interface Science
700.
- Abstract
The peptide Ac-KGSFSIQYTYHVD-CONH₂ (KD), derived from residues 37–49 of human semenogelin I, forms a pH-responsive hydrogel in an aqueous environment with tunable mechanical properties that evolve over time. We hypothesize that KD self-assembles into a hydrogel through a pH-dependent mechanism involving predominantly a change in histidine protonation state, leading to structural transformations that modulate its mechanical properties. Time-resolved nuclear magnetic resonance (NMR) spectroscopy and cryo-transmission electron microscopy (cryo-TEM) were employed to elucidate the gelation process and structural evolution of KD. pH measurements were conducted to monitor changes in peptide interactions during self-assembly. Rheological... (More)
The peptide Ac-KGSFSIQYTYHVD-CONH₂ (KD), derived from residues 37–49 of human semenogelin I, forms a pH-responsive hydrogel in an aqueous environment with tunable mechanical properties that evolve over time. We hypothesize that KD self-assembles into a hydrogel through a pH-dependent mechanism involving predominantly a change in histidine protonation state, leading to structural transformations that modulate its mechanical properties. Time-resolved nuclear magnetic resonance (NMR) spectroscopy and cryo-transmission electron microscopy (cryo-TEM) were employed to elucidate the gelation process and structural evolution of KD. pH measurements were conducted to monitor changes in peptide interactions during self-assembly. Rheological studies, including oscillatory and stationary rheology, were performed to assess the mechanical properties of the hydrogel under varying pH conditions. A gradual pH drift was observed, associated with a modulation of the ionizable histidine side chain pKa as KD assembled into β-sheet fibrils, integrating into the hydrogel network. Cryo-TEM analysis revealed two distinct nanostructural morphologies: fibrils and twisted curly nanostructures with uniform dimensions, demonstrating micro- and nanoscale transformations over time. Rheological measurements indicated a substantial increase in the elastic modulus as the pH shifted, confirming the dynamic tunability of the hydrogel. Under buffered conditions, KD rapidly formed hydrogels within the experimental dead time, indicating its quick responsiveness to environmental changes. These results provide mechanistic insights into the time-dependent self-assembly of KD and highlight its potential as a pH-tunable hydrogel for therapeutic applications, paving the way for the rational design of next-generation peptide-based biomaterials.
(Less)
- author
- Gentile, Luigi
LU
; Frohm, Birgitta
LU
; Malmendal, Anders
LU
; Åkerfeldt, Karin S.
LU
; Olsson, Ulf
LU
and Linse, Sara
LU
- organization
- publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Hydrogelation, Peptide, pH-responsive, Self-assembly, Stimuli-responsive
- in
- Journal of Colloid and Interface Science
- volume
- 700
- article number
- 138615
- publisher
- Academic Press
- external identifiers
-
- scopus:105012380146
- pmid:40773884
- ISSN
- 0021-9797
- DOI
- 10.1016/j.jcis.2025.138615
- language
- English
- LU publication?
- yes
- id
- 3fe5c397-12d3-4856-a24b-1ba4fe67b73a
- date added to LUP
- 2025-10-22 14:52:51
- date last changed
- 2025-10-22 14:53:50
@article{3fe5c397-12d3-4856-a24b-1ba4fe67b73a,
abstract = {{<p>The peptide Ac-KGSFSIQYTYHVD-CONH₂ (KD), derived from residues 37–49 of human semenogelin I, forms a pH-responsive hydrogel in an aqueous environment with tunable mechanical properties that evolve over time. We hypothesize that KD self-assembles into a hydrogel through a pH-dependent mechanism involving predominantly a change in histidine protonation state, leading to structural transformations that modulate its mechanical properties. Time-resolved nuclear magnetic resonance (NMR) spectroscopy and cryo-transmission electron microscopy (cryo-TEM) were employed to elucidate the gelation process and structural evolution of KD. pH measurements were conducted to monitor changes in peptide interactions during self-assembly. Rheological studies, including oscillatory and stationary rheology, were performed to assess the mechanical properties of the hydrogel under varying pH conditions. A gradual pH drift was observed, associated with a modulation of the ionizable histidine side chain pKa as KD assembled into β-sheet fibrils, integrating into the hydrogel network. Cryo-TEM analysis revealed two distinct nanostructural morphologies: fibrils and twisted curly nanostructures with uniform dimensions, demonstrating micro- and nanoscale transformations over time. Rheological measurements indicated a substantial increase in the elastic modulus as the pH shifted, confirming the dynamic tunability of the hydrogel. Under buffered conditions, KD rapidly formed hydrogels within the experimental dead time, indicating its quick responsiveness to environmental changes. These results provide mechanistic insights into the time-dependent self-assembly of KD and highlight its potential as a pH-tunable hydrogel for therapeutic applications, paving the way for the rational design of next-generation peptide-based biomaterials.</p>}},
author = {{Gentile, Luigi and Frohm, Birgitta and Malmendal, Anders and Åkerfeldt, Karin S. and Olsson, Ulf and Linse, Sara}},
issn = {{0021-9797}},
keywords = {{Hydrogelation; Peptide; pH-responsive; Self-assembly; Stimuli-responsive}},
language = {{eng}},
publisher = {{Academic Press}},
series = {{Journal of Colloid and Interface Science}},
title = {{Charge regulation in peptide self-assembly and hydrogelation}},
url = {{http://dx.doi.org/10.1016/j.jcis.2025.138615}},
doi = {{10.1016/j.jcis.2025.138615}},
volume = {{700}},
year = {{2025}},
}