Helix versus coil polypeptide macromers: gel networks with decoupled stiffness and permeability

• Main Authors: Oelker, Abigail M. (Contributor), Morey, Shannon M. (Contributor), Griffith, Linda G. (Contributor), Hammond, Paula T. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor)
• Format: Article
• Language: English
• Published: Royal Society of Chemistry, 2014-08-19T18:33:15Z.
• Subjects: Article
• Online Access: Get fulltext

 As a platform for investigating the individual effects of substrate stiffness, permeability, and ligand density on cellular behavior, we developed a set of hydrogels with stiffness tuned by polymer backbone rigidity, independent of cross-link density and concentration. Previous studies report that poly(propargyl-L-glutamate) (PPLG), synthesized by ring-opening polymerization of the N-carboxy anhydride of γ-propargyl-L-glutamate (γpLglu), adopts a rigid a-helix conformation: we hypothesized that a random copolymer (PPDLG) with equal amounts of γpLglu and γ-propargyl-D-glutamate (γpDglu) monomers would exhibit a more flexible random coil conformation. The resulting macromers exhibited narrow molecular weight distributions (PDI = 1.15) and were grafted with ethylene glycol groups using a highly efficient "click" azide/alkyne cycloaddition reaction with average grafting efficiency of 97% for PPLG and 85% for PPDLG. The polypeptide secondary structure, characterized via circular dichroism spectroscopy, FTIR spectroscopy, and dynamic light scattering, is indeed dependent upon monomer chirality: PPLG exhibits an α-helix conformation while PPDLG adopts a random coil conformation. Hydrogel networks produced by cross-linking either helical or random coil polypeptides with poly(ethylene glycol) (PEG) were analyzed for amount of swelling, gelation efficiency, and permeability to a model protein. In addition, the elastic modulus of helical and coil polypeptide gels was determined by AFM indentation in fluid. Importantly, we found that helical and coil polypeptide gels exhibited similar swelling and permeability but different stiffnesses, which correspond to predictions from the theory of semi-flexible chains.