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Nanofibrous Peptide Hydrogels Leveraging Histidine to Modulate pH-Responsive Supramolecular Assembly and Antibody Release

Saenz, Gabriel ; Pogostin, Brett H. LU ; Cole, Carson C. ; Agrawal, Anushka ; Chew-Martinez, Danielle ; Dubackic, Marija LU ; Pal, Antara LU ; Olsson, Ulf LU ; McHugh, Kevin J. and Hartgerink, Jeffrey D. (2025) In Biomacromolecules 26(1). p.490-502
Abstract

In this work, we investigate the pH-responsive behavior of multidomain peptide (MDP) hydrogels containing histidine. Small-angle X-ray scattering confirmed that MDP nanofibers sequester nonpolar residues into a hydrophobic core surrounded by a shell of hydrophilic residues. MDPs with histidine on the hydrophilic face formed nanofibers at all pH values tested, but the morphology of the fibers was influenced by the protonation state and the location of histidine in the MDP sequence. MDPs with histidine residues within the hydrophobic face disassemble below physiological pH and form nanofibers at higher pH. Taking advantage of their stimulus-triggered behavior, an anti-PD-1 antibody was loaded into histidine MDP hydrogels to examine... (More)

In this work, we investigate the pH-responsive behavior of multidomain peptide (MDP) hydrogels containing histidine. Small-angle X-ray scattering confirmed that MDP nanofibers sequester nonpolar residues into a hydrophobic core surrounded by a shell of hydrophilic residues. MDPs with histidine on the hydrophilic face formed nanofibers at all pH values tested, but the morphology of the fibers was influenced by the protonation state and the location of histidine in the MDP sequence. MDPs with histidine residues within the hydrophobic face disassemble below physiological pH and form nanofibers at higher pH. Taking advantage of their stimulus-triggered behavior, an anti-PD-1 antibody was loaded into histidine MDP hydrogels to examine pH-dependent differences in payload delivery in vitro. Hydrogels composed of MDPs with histidine on the hydrophilic face demonstrated pH-dependent payload retention. Additionally, they showed significantly slower antibody release and reduced antibody diffusion rates in vitro compared to MDP hydrogels lacking histidine.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biomacromolecules
volume
26
issue
1
pages
13 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:39801309
  • scopus:85214936058
ISSN
1525-7797
DOI
10.1021/acs.biomac.4c01296
language
English
LU publication?
yes
id
b1ff8b20-058f-43ca-af5d-d2333bf6d77b
date added to LUP
2025-03-12 14:53:56
date last changed
2025-07-17 10:57:14
@article{b1ff8b20-058f-43ca-af5d-d2333bf6d77b,
  abstract     = {{<p>In this work, we investigate the pH-responsive behavior of multidomain peptide (MDP) hydrogels containing histidine. Small-angle X-ray scattering confirmed that MDP nanofibers sequester nonpolar residues into a hydrophobic core surrounded by a shell of hydrophilic residues. MDPs with histidine on the hydrophilic face formed nanofibers at all pH values tested, but the morphology of the fibers was influenced by the protonation state and the location of histidine in the MDP sequence. MDPs with histidine residues within the hydrophobic face disassemble below physiological pH and form nanofibers at higher pH. Taking advantage of their stimulus-triggered behavior, an anti-PD-1 antibody was loaded into histidine MDP hydrogels to examine pH-dependent differences in payload delivery in vitro. Hydrogels composed of MDPs with histidine on the hydrophilic face demonstrated pH-dependent payload retention. Additionally, they showed significantly slower antibody release and reduced antibody diffusion rates in vitro compared to MDP hydrogels lacking histidine.</p>}},
  author       = {{Saenz, Gabriel and Pogostin, Brett H. and Cole, Carson C. and Agrawal, Anushka and Chew-Martinez, Danielle and Dubackic, Marija and Pal, Antara and Olsson, Ulf and McHugh, Kevin J. and Hartgerink, Jeffrey D.}},
  issn         = {{1525-7797}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{490--502}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Biomacromolecules}},
  title        = {{Nanofibrous Peptide Hydrogels Leveraging Histidine to Modulate pH-Responsive Supramolecular Assembly and Antibody Release}},
  url          = {{http://dx.doi.org/10.1021/acs.biomac.4c01296}},
  doi          = {{10.1021/acs.biomac.4c01296}},
  volume       = {{26}},
  year         = {{2025}},
}