Change in Viscoelasticity of the Hemoglobin-Introduced Supramolecular Polymer Hydrogel in Response to pH, Temperature, and Oxygen Partial Pressure.

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.