Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells

Haines-Butterick, Lisa A.; Rajagopal, Karthikan; Branco, Monica C.; Salick, Daphne A.; Rughani, Ronak V.; Pilarz, Matthew; Lamm, Matthew S.; Pochan, Darrin J.; Schneider, Joel P.

doi:10.1073/pnas.0701980104

Cited by 601 publications

(765 citation statements)

References 44 publications

Supporting

Mentioning

739

Contrasting

Unclassified

Order By: Relevance

“…In particular, mucin-mucin adhesive interactions (that cause bundling) may be important for rapid recovery of the bulk viscoelasticity of polymer gels after a large strain (1,46). Multiple hydrophobic interactions between mucin fibers may therefore enable mucus to be cleared efficiently by cough clearance (slower recovery of elasticity, which may occur in the absence of these adhesive interactions, might cause mucus to drip back into the lungs).…”

Section: Discussionmentioning

confidence: 99%

Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses

Lai

Wang²,

Hida³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

333

343

View full text Add to dashboard Cite

The mechanisms by which mucus helps prevent viruses from infecting mucosal surfaces are not well understood. We engineered non-mucoadhesive nanoparticles of various sizes and used them as probes to determine the spacing between mucin fibers (pore sizes) in fresh undiluted human cervicovaginal mucus (CVM) obtained from volunteers with healthy vaginal microflora. We found that most pores in CVM have diameters significantly larger than human viruses (average pore size 340 ± 70 nm; range approximately 50–1800 nm). This mesh structure is substantially more open than the 15–100-nm spacing expected assuming mucus consists primarily of a random array of individual mucin fibers. Addition of a nonionic detergent to CVM caused the average pore size to decrease to 130 ± 50 nm. This suggests hydrophobic interactions between lipid-coated “naked” protein regions on mucins normally cause mucin fibers to self-condense and/or bundle with other fibers, creating mucin “cables” at least three times thicker than individual mucin fibers. Although the native mesh structure is not tight enough to trap most viruses, we found that herpes simplex virus (approximately 180 nm) was strongly trapped in CVM, moving at least 8,000-fold slower than non-mucoadhesive 200-nm nanoparticles. This work provides an accurate measurement of the pore structure of fresh, hydrated ex vivo CVM and demonstrates that mucoadhesion, rather than steric obstruction, may be a critical protective mechanism against a major sexually transmitted virus and perhaps other viruses.

show abstract

Section: Discussionmentioning

confidence: 99%

Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses

Lai

Wang²,

Hida³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

333

343

View full text Add to dashboard Cite

show abstract

“…There are a number of successful examples of hydrogels designed for tissueengineering and drug-delivery applications that use functional protein domains to obtain structural responsiveness to environmental cues (2)(3)(4). These examples include responsiveness to pH (5), temperature (6), shear stress (7), and ligand binding (8,9) among others (refs. 2 and 10; ref.…”

mentioning

confidence: 99%

Bioelectrocatalytic hydrogels from electron-conducting metallopolypeptides coassembled with bifunctional enzymatic building blocks

Wheeldon

Gallaway

Barton

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Here, we present two bifunctional protein building blocks that coassemble to form a bioelectrocatalytic hydrogel that catalyzes the reduction of dioxygen to water. One building block, a metallopolypeptide based on a previously designed triblock polypeptide, is electron-conducting. A second building block is a chimera of artificial ␣-helical leucine zipper and random coil domains fused to a polyphenol oxidase, small laccase (SLAC). The metallopolypeptide has a helix-random-helix secondary structure and forms a hydrogel via tetrameric coiled coils. The helical and random domains are identical to those fused to the polyphenol oxidase. Electron-conducting functionality is derived from the divalent attachment of an osmium bis-bipyrdine complex to histidine residues within the peptide. Attachment of the osmium moiety is demonstrated by mass spectroscopy (MS-MALDI-TOF) and cyclic voltammetry. The structure and function of the ␣-helical domains are confirmed by circular dichroism spectroscopy and by rheological measurements. The metallopolypeptide shows the ability to make electrical contact to a solid-state electrode and to the redox centers of modified SLAC. Neat samples of the modified SLAC form hydrogels, indicating that the fused ␣-helical domain functions as a physical cross-linker. The fusion does not disrupt dimer formation, a necessity for catalytic activity. Mixtures of the two building blocks coassemble to form a continuous supramolecular hydrogel that, when polarized, generates a catalytic current in the presence of oxygen. The specific application of the system is a biofuel cell cathode, but this protein-engineering approach to advanced functional hydrogel design is general and broadly applicable to biocatalytic, biosensing, and tissue-engineering applications.biocatalysis ͉ biofuel cell ͉ biomaterial ͉ laccase ͉ protein P rotein engineering provides the tool set to design and produce peptides and proteins that form the building blocks of new bio-inspired materials. The tool set allows for the manipulation of natural and artificial DNA sequences encoding the peptides or proteins of interest, and the subsequent biological production of the translated products. The methodology is powerful in that it allows for exact control over the identity and sequence of each residue and, consequently, the structural folding patterns of the resultant peptides or proteins (1). And, just as function stems from structure, it is also controlled within the protein-engineering scheme of materials design. There are a number of successful examples of hydrogels designed for tissueengineering and drug-delivery applications that use functional protein domains to obtain structural responsiveness to environmental cues (2-4). These examples include responsiveness to pH (5), temperature (6), shear stress (7), and ligand binding (8, 9) among others (refs. 2 and 10; ref. 3 and references therein). A wider range of applications, such as bioelectrocatalysis and biosensing, will benefit from the advantages of protein-based materials design pr...

show abstract

“…Environmental stimuli including pH [16][17][18][19], ionic strength and/or metal ions [18,[20][21][22], temperature [23], light [24] and enzyme-triggers [25], provide powerful approaches for modulating hydrogelation. Furthermore, introduction of microenvironment-sensitive amino acid residues into peptide sequences is also an important strategy for controlling peptide self-assembly and hydrogelation [9,[26][27][28].…”

mentioning

confidence: 99%

“…Peptide hydrogels have been actively exploited for a variety of biomedical applications such as cell culture, regenerative medicine, controlled drug and gene delivery [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Most peptide hydrogels arise from the entanglement of selfassembled nanoobjects such as nanofibers and nanotubes.…”

mentioning

confidence: 99%

Redox modulated hydrogelation of a self-assembling short peptide amphiphile

Cao

Fan

et al. 2012

Chin. Sci. Bull.

View full text Add to dashboard Cite

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.

show abstract

Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells

Cited by 601 publications

References 44 publications

Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses

Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses

Bioelectrocatalytic hydrogels from electron-conducting metallopolypeptides coassembled with bifunctional enzymatic building blocks

Redox modulated hydrogelation of a self-assembling short peptide amphiphile

Contact Info

Product

Resources

About