Redox modulated hydrogelation of a self-assembling short peptide amphiphile

Abstract

Hydrogels resulting from the self-assembly of small peptides are smart nanobiomaterials as their nanostructuring can be readily tuned by environmental stimuli such as pH, ionic strength and temperature, thereby favoring their practical applications. This work reports experimental observations of formation of peptide hydrogels in response to the redox environment. Ac-I 3 K-NH 2 is a short peptide amphiphile that readily self-assembles into long nanofibers and its gel formation occurs at concentrations of about 10 mmol/L. Introduction of a Cys residue into the hydrophilic region leads to a new molecule, Ac-I 3 CGK-NH 2 , that enables the formation of disulfide bonds between self-assembled nanofibers, thus favoring cross-linking and promoting hydrogel formation. Under oxidative environment, Ac-I 3 CGK-NH 2 formed hydrogels at much lower concentrations (even at 0.5 mmol/L). Furthermore, the strength of the hydrogels could be easily tuned by switching between oxidative and reductive conditions and time. However, AFM, TEM, and CD measurements revealed little morphological and structural changes at molecular and nano dimensions, showing no apparent influence arising from the disulfide bond formation.peptide amphiphiles, self-assembly, hydrogelation, redox stimuli Citation:Cao C H, Cao M W, Fan H M, et al. Redox modulated hydrogelation of a self-assembling short peptide amphiphile.

Supramolecular Hydrogelators and Hydrogels: From Soft Matter to Molecular Biomaterials

“…Replacing the Cys by a Met residue allows the formation of nanofibers at 1.7 mM, but fails to generate any hydrogels. 115 Nilsson et al synthesized a series of capped octapeptides (Ac-XKXKXKXK-NH 2 ; X = Val ( 270a ), Ile ( 270b ), Phe ( 270c ), F5 Phe ( 270d ), and cyclohexylalanine (Cha) ( 270e )) that are composed of alternating hydrophobic residues (Val) and positively charged residues (Lys). At 8 mM, 270a is too hydrophilic to form a hydrogel, but 270b , 270c , 270d , or 270e self-assembles in water to form a hydrogel.…”

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

“…A self‐assembling peptide sequence, Ac‐C(FKFE) 2 CG‐NH 2 , cyclized via disulfide bonding of the flanking cysteine residues has been shown to self‐assemble into fibrillar structures upon reduction of the disulphide bond . In another report, Ac‐I 3 CGK‐NH 2 , a cysteine‐containing small peptide, formed hydrogels at low concentrations under an oxidative environment, where their mechanical properties have been tuned via degree of oxidation . Of these chemical stimuli‐responsive supramolecular hydrogels, redox‐responsive supramolecular hydrogels have been extensively studied, especially for their self‐healing property and potential applications as actuators .…”

“…[162] In another report, Ac-I 3 CGK-NH 2 , a cysteine-containing small peptide, formed hydrogels at low concentrations under an oxidative environment, where their mechanical properties have been tuned via degree of oxidation. [167] Of these chemical stimuli-responsive supramolecular hydrogels, redox-responsive supramolecular hydrogels have been extensively studied, especially for their self-healing property and potential applications as actuators. [168,169] Using redox stimuli-triggered gel–sol transition of olsalazine-containing supramolecular hydrogel, a site-specific delivery of anti-inflammatory drug was shown by Li et al [170] In another study, Wojciechowski et al have shown temporal control over transient gelation of redox-triggered supramolecular hydrogelators by tuning the competing kinetics of dissolution and gelation, thus expanding the scope of chemical stimuli-responsive supramolecular hydrogels.…”

Biomaterials based on noncovalent interactions of small molecules

“…Increased ionic strength in some cases also triggers self-assembly, as reported by Goldberger et al (2011[ 29 ]) that 5 mM Ca 2+ renders morphological transition to form nanofibers. In addition, introducing functional groups into precursors allow certain chemical reactions, such as hydrolysis (Zhao et al, 2011[ 114 ]), redox reactions (Chen et al, 2012[ 8 ]; Cao et al, 2012[ 7 ]), and photochemical reactions (Yamamoto et al,1999[ 99 ]), to take place, which are useful types of triggering mechanisms for controlling intermolecular interactions and initiating self-assembly.…”