Peptide stereocomplex cross-links for polymer hydrogels

Stereocomplexation, or stereochemistry-directed complexation between complementary stereoregular macromolecules such as polymers and peptides, brings about remarkable changes in the thermomechanical properties and stability of materials. Peptide stereocomplexes tie together these merits of stereocomplexation with the vast compositional space and biological function of peptides, and therefore are compelling building blocks of highly tunable, functional materials. In this work, we introduce peptide stereocomplexes as cross-links in polymer hydrogels. Attaching either l- or d-peptides to 4-arm PEG furnishes conjugates that are soluble in aqueous buffer, while their 1 : 1 blends form hydrogels at or above 7.5% (w/v). Increasing conjugate concentration increases both shear storage modulus (<i>G</i>') and the intensity of the characteristic β-sheet infrared absorption at 1630 cm^-1, highlighting the importance of peptide secondary structure for gelation. These gels, having peptide stereocomplexes as cross-links, strain stiffen up to nearly 50% strain, then soften at higher strains. Despite the crystalline nature of stereocomplexes, these gels display dynamic behavior: after application and removal of high strain, the gels recover partially, with 10-50% recovery of <i>G</i>' after the first cycle and 50-70% in subsequent cycles. Moreover, the peptide stereocomplex cross-links imbue proteolytic stability, with nearly 80% of conjugates remaining intact after a 1 h incubation with Proteinase K, compared to just ∼40% of the l-conjugates. We anticipate that the material platform and combination of characterization methods presented here will readily extend to studying other peptides sequences, so as to leverage the full range of peptide design space and accelerate the development and implementation of peptide stereocomplexes to control hydrogel properties, function, and lifetime.