Change in Viscoelasticity of the Hemoglobin-Introduced Supramolecular Polymer Hydrogel in Response to pH,...

Hemoglobin (Hb) compartmentalized within red blood cells plays a key role in respiration by reversible oxygen (O₂) binding at the site of ferrous heme iron. The stable α₂β₂ tetrameric quaternary structure of Hb reversibly dissociates into two αβ dimers (α₂β₂ ⇌ 2αβ). The α₂β₂ structure stability depends on pH and temperature, and on the state of heme, such as iron valence, ligands, and O₂ release. For this work, we synthesized a supramolecular polymer hydrogel by conjugating the β-subunits of Hb with four-armed 40 kDa PEG. The resulting gel has physical cross-links via the association of Hb subunits. It therefore undergoes changes in viscoelasticity upon multiple external stimuli, including changes in pH, temperature, and the O₂ partial pressure (pO₂). It is noteworthy that the characteristic relaxation time τ and the zero-shear viscosity η₀ both increase ca. 100-fold in response to O₂ dissociation occurring with lower pO₂. This paper is the first to present a synthetic hydrogel that can switch the viscoelasticity by binding and releasing O₂, demonstrating this "respirable" gel as a promising O₂-responsive smart material.