Thermal Anomaly of Erythrocyte Osmotic Fragility and Aquaporin Function at Body Temperature

The recently proposed Interfacial Water Quantum Transition (IWQ) model presents a novel framework for functional changes in proteins at critical temperatures. Building on this, we hypothesized that red blood cell (RBC) osmotic fragility (OF) and aquaporin (AQP) function might exhibit similar transitions. We assessed the osmotic resistance of human and chicken RBCs across 24–50 °C. Mean corpuscular fragility (MCF 50 ) was obtained by logistic curve fitting. In human RBCs, MCF 50 consistently decreased with increasing temperature in whole blood, washed RBCs, and HgCl 2 -treated (known to reduce AQP water permeability) RBCs. Washed RBCs were more fragile, indicating a protective role of plasma proteins. An abrupt MCF 50 drop at T c = 36.0 ± 0.4 °C in washed RBCs abolished group differences, suggesting a functional transition at the critical temperature, T C . For chicken RBCs at T c = 41.0 ± 0.5 °C, a phase transition-like decrease in MCF 50 was observed, where it dropped from 0.32 at 40 °C to 0.28 at 41 °C. This decrease remained consistent above T C , unlike the peak-like curve shape in human RBCs around T C . These results suggest a species-specific, temperature-triggered anomaly and its osmotic regulation mechanism. The OF transitions found align with known hemoglobin temperature transitions, highlighting the physiological relevance of thermo-sensitive protein-water interactions. The findings of this study could foster the understanding of temperature-regulated water transport in red blood cells and for the development of AQP-specific applications in transfusion medicine or bioengineered membranes. • Species-specific fragility transitions occur at critical temperatures. • OF temperature-transitions align with hemoglobin shifts predicted by IWQ model. • Critical temperatures match species specific body temperatures. • Hemoglobin-water interactions and temperature contribute to osmotic responsiveness. • Proteins sense, and water sets the critical physiological temperatures.