Reversible Stiffening Transition in β-Hairpin Hydrogels Induced by Ion Complexation

Abstract

We have previously shown that properly designed lysine and valine-rich peptides undergo a random coil to beta-hairpin transition followed by intermolecular self-assembly into a fibrillar hydrogel network only after the peptide solutions are heated above the intramolecular folding transition temperature. Here we report that these hydrogels also undergo a stiffening transition as they are cooled below a critical temperature only when boric acid is used to buffer the peptide solution. This stiffening transition is characterized by rheology, dynamic light scattering, and small angle neutron scattering. Rheological measurements show that the stiffening transition causes an increase in the hydrogel storage modulus (G') by as much as 1 order of magnitude and is completely reversible on subsequently raising the temperature. Although this reversible transition exhibits rheological properties that are similar to polyol/borax solutions, the underlying mechanism does not involve hydroxyl-borate complexation. The stiffening transition is mainly caused by the interactions between lysine and boric acid/borate anion and is not driven by the changes in the secondary structure of the beta-hairpin peptide. Addition of glucose to boric acid and peptide solution disrupts the stiffening transition due to competitive glucose-borate complexation.

Calcium Ions to Cross-Link Supramolecular Nanofibers to Tune the Elasticity of Hydrogels over Orders of Magnitude

“…49 Thus, our results might fundamentally differ with the case pyromellitamide organogels. Second, the crosslink also can occur in the carboxyl group of individual fibers, 50 which increases the storage modulus of resulted hydrogel upon the addition of calcium ion. This result clearly differs from the increase of the mechanical properties of the hydrogels caused by the increase of the concentration of the hydrogelators, also distincts from the rigid hydrogel formed by intermolecular folding of synthetic peptide, 51 but it resembles to a phenomenon only occurring in the case of actin 52 that the increase of the stiffness of a hydrogel via solely changing the amount of calcium ion.…”

Nanomaterials for cartilage tissue engineering

“…These peptides are composed of alternating hydrophilic and hydrophobic residues fl anking an intermittent tetrapetide and dissolve in aqueous solutions in random coil conformations. Under specifi c stimuli, molecules can be triggered to fold into a β -hairpin conformation that undergoes rapid self-assembly into a β -sheet-rich, highly cross-linked hydrogel (Schneider et al ., 2002 ;Pochan et al ., 2003 ;Ozbas et al ., 2004, Haines et al ., 2005Haines-Butterick et al ., 2007 ). These hydrogels supported cell growth and can be further tailored to have specifi c and controlled biodegradation rates by incorporation of sequences cleaveable by matrix metalloproteinase-13 (Giano et al ., 2011 ).…”

Modular self-assembling biomaterials for directing cellular responses

“…This latter example demonstrated the modularity of this approach, in which mechanical properties and cell binding could be controlled in separate, orthogonal, easily combined ways. Matrix mechanics in self-assemblies of peptides or peptide-amphiphiles have also been controlled through the formation of disulfide bonds, 18 through primary sequence variations, 35 by ion complexation, 36 and by adjusting the concentration of the self-assembled species, 37 though the latter example is less modular because cell attachment points, porosity, and other biophysical aspects may change with varying peptide concentration. It is expected that advancing sophistication in the ability to regulate the mechanical environments surrounding cells will continue to improve the ability to direct desirable cell and tissue responses.…”