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-I3K-NH2 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-I3CGK-NH2, that enables the formation of disulfide bonds between self-assembled nanofibers, thus favoring cross-linking and promoting hydrogel formation. Under oxidative environment, Ac-I3CGK-NH2 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.
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Holmes T C, de Lacalle S, Su X, et al. Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds. Proc Natl Acad Sci USA, 2000, 97: 6728–6733
Kisiday J, Jim M, Kurz B, et al. Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair. Proc Natl Acad Sci USA, 2002, 99: 9996–10001
Silva G A, Czeisler C, Niece K L, et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science, 2004, 303: 1352–1355
Kretsinger J K, Haines L A, Ozbas B, et al. Cytocompatibility of self-assembled beta-hairpin peptide hydrogel surfaces. Biomaterials, 2005, 26: 5177–5186
Beniash E, Hartgerink J D, Storrie H, et al. Self-assembling peptide amphiphile nanofiber matrices for cell entrapment. Acta Biomater, 2005, 1: 387–397
Gelain F, Bottai D, Vescovi A, et al. Designer self-assembling peptide nanofiber scaffolds for adult mouse neural stem cell 3-dimensional cultures. PLoS One, 2006, 1: e119
Nagai Y, Unsworth L D, Koutsopoulos S, et al. Slow release of moleculesin self-assembling peptide nanofiber scaffold. J Control Release, 2006, 115: 18–25
Jayawarna V, Ali M, Jowitt T A, et al. Nanostructured hydrogels for three-dimensional cell culture through self-assembly of fluorenylmethoxycarbonyldipeptides. Adv Mater, 2006, 18: 611–614
Haines-Butterick L, Rajagopal K, Branco M, et al. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proc Natl Acad Sci USA, 2007, 104: 7791–7796
Jung J P, Nagaraj A K, Fox E K, et al. Co-assembling peptides as defined matrices for entothelias cells. Biomaterials, 2009, 30: 2400–2410
Gelain F, Unsworth L D, Zhang S. Slow and sustained release of active cytokines from self-assembling peptide scaffolds. J Control Release, 2010, 145: 231–239
Galler K M, Aulisa L, Regan K R, et al. Self-assembling multidomain peptide hydrogels: Designed susceptibility to enzymatic cleavage allows enhanced cell migration and spreading. J Am Chem Soc, 2010, 132: 3217–3223
Williams R J, Hall T E, Glattauer V, et al. The in vivo performance of an enzyme-assisted self-assembled peptide/protein hydorgel. Biomaterials, 2011, 3: 5304–5310
Bakota E L, Wang Y, Danesh F R, et al. Injectable multidomain peptide nanofiber hydrogel as a delivery agent for stem cell secretome. Biomacromolecules, 2011, 12: 1651–1657
Bulut S, Erkal T S, Toksoz S, et al. Slow release and delivery of antisense oligonucleotide drug by self-assembled peptide amphiphile nanofibers. Biomacromolecues, 2011, 12: 3007–3014
Hartgerink J D, Beniash E, Stupp S I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science, 2001, 294: 1684–1688
Schneider J P, Pochan D J, Ozbas B, et al. Responsive hydrogels from the intramolecular folding and self-assembly of a designed peptide. J Am Chem Soc, 2002, 124: 15030–15037
Hartgerink J D, Beniash E, Stupp S I. Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials. Proc Natl Acad Sci USA, 2002, 99: 5133–5138
Rajagopal K, Lamm M S, Haines-Butterick L A, et al. Tuning the pH responsiveness of ?-hairpin peptide folding, self-assembly, and hydrogel material formation. Biomacromolecules, 2009, 10: 2619–2625
Zhang S, Holmes T, Lockshin C, et al. Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc Natl Acad Sci USA, 1993, 90: 3334–3338
Ozbas B, Kretsinger J, Rajagopal K, et al. Salt-triggered peptide folding and consequent self-assembly into hydrogels with tunable modulus. Macromolecules, 2004, 37: 7331–7337
Micklitsch C M, Knerr P J, Branco M C, et al. Zinc-triggered hydrogelation of a self-assembling β-hairpin peptide. Angew Chem Int Ed, 2011, 123: 1615–1617
Pochan D J, Schneider J P, Kretsinger J, et al. Thermally reversible hydrogels via intramolecular folding and consequent self-assembly of a de novo designed peptide. J Am Chem Soc, 2003, 125: 11802–11803
Haines L A, Rajagopal K. Ozbas B, et al. Light-activated hydrogel formation via the triggered folding and self-assembly of a designed peptide. J Am Chem Soc, 2005, 127: 17025–17029
Toledano S, Williams R J, Jayawarna V, et al. Enzyme-triggered self-assembly of peptide hydrogels via reversed hydrolysis. J Am Chem Soc, 2006, 128: 1070–1071.
Caplan M R, Schwartzfarb E M, Zhang S, et al. Control of self-assembling oligopeptide matrix formation through systematic variation of amino acid sequence. Biomaterials, 2002, 23: 219–227
Bowerman C J, Nilsson B L. A reductive trigger for peptide self-assembly and hydrogelation. J Am Chem Soc, 2010, 132: 9526–9527
Jung J P, Jones J L, Cronier S A, et al. Modulating the mechanical properties of self-assembled peptide hydrogels via native chemical ligation. Biomaterials, 2008, 29: 2143–2151
Xu H, Wang Y M, Ge X, et al. Twisted nanotubes formed from ultrashort amphiphilic peptide I3K and their templating for the fabrication of silica nanotubes. Chem Mater, 2010, 22: 5165–5173
Xu H, Wang J, Han S Y, et al. Hydrophobic-region-Induced transitions in self-assembled peptide nanostructures. Langmuir, 2009, 25: 4115–4123
Wang J, Han S Y, Meng G, et al. Dynamic self-assembly of surfactant-like peptides A6K and A9K. Soft Matter, 2009, 5: 3870–3878
Chen C X, Pan F, Zhang S Z, et al. Antibacterial activities of short designer peptide: A link between propensity for nanostructuring and capacity for membrane destabilization. Biomacromolecules, 2010, 11: 402–411
Han S Y, Cao S S, Wang Y M, et al. Self-assembly of short peptide amphiphiles: The cooperative effect of hydrophobic interaction and hydrogen bonding. Chem Eur J, 2011, 17: 13095–13102
Ellman G L. Tissue sulfhydryl groups. Arch Biochem Biophys, 1959, 82: 70–77
Akaji K, Tatsumi T, Yoshida M, et al. Disulfide bond formation using the silyl chloride-sulfoxide system for the synthesis of a cystine peptide. J Am Chem Soc, 1992, 114: 4137–4143
Schneider J P, Pochan D J, Ozbas B, et al. Responsive hydrogels from the intramolecular folding and self-assembly of a designed peptide. J Am Chem Soc, 2002, 124: 15030–15037
Barth A, Zscherp C. What vibrations tell about proteins. Q Rev Biophys, 2002, 35: 369–430
Yan H, Saiani A, Gough J E, et al. Thermoreversible protein hydrogel as cell scaffold. Biomacromolecules, 2006, 7: 2776–2782
Krysmann M J, Castelletto V, Kelarakis A, et al. Self-assembly and hydrogelation of an amyloid peptide fragment. Biochemistry, 2008, 47: 4597
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Cao, C., Cao, M., Fan, H. et al. Redox modulated hydrogelation of a self-assembling short peptide amphiphile. Chin. Sci. Bull. 57, 4296–4303 (2012). https://doi.org/10.1007/s11434-012-5487-2
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DOI: https://doi.org/10.1007/s11434-012-5487-2