Thermodynamic Frontiers in Hemoglobin-Inspired Polymer Science for Diagnosis and Modulation of Neurodegenerative Diseases.

The thermodynamic logic underlying hemoglobin's cooperative binding and reversible conformational transitions offers a powerful conceptual model for reimagining polymer design in neurodegenerative medicine. In this review perspective, we outline a unified thermodynamic framework that connects molecular energetics, polymer science, and pathological protein aggregation. We discuss how hemoglobin's allosteric adaptability, enthalpy-entropy compensation, and redox responsiveness can inspire polymers capable of sensing and reshaping the free-energy landscapes that govern amyloid formation. Drawing on evidence from protein thermodynamics, polymer chemistry, and neurobiological systems, we propose design principles for adaptive, hemoglobin-inspired polymers that act as artificial chaperones, materials capable of modulating aggregation equilibria, restoring proteostatic balance, and integrating diagnostic and therapeutic functions. This article defines an emerging field at the intersection of thermodynamic polymer science and neurodegeneration, where materials are not passive carriers but active regulators of molecular energy landscapes.