Conformation-driven mechanical duality: Viscoelastic and poroelastic switching in protein hydrogels

Bovine serum albumin (BSA) hydrogels reveal a fundamental mechanical duality in protein-based biomaterials. Using chemically crosslinked BSA networks as a model system, we show that the same hydrogel can dissipate stress through two distinct regimes depending on protein conformation. Native BSA hydrogels exhibit viscoelastic relaxation, governed by unfolding of protein domains, whereas chemically denatured BSA hydrogels display poroelastic dissipation, dominated by solvent migration through the deformed matrix. This denaturation-driven switch between viscoelastic and poroelastic mechanics highlights the direct coupling between protein structure and macroscopic energy dissipation. By disentangling these two dissipative modes within a single material platform, our findings provide a conceptual framework for designing protein-based hydrogels with state-dependent mechanical responses, with potential applications in biomaterials, mechanobiology, and soft matter engineering. STATEMENT OF SIGNIFICANCE: This study reveals how the folding state of proteins controls the way protein-based hydrogels dissipate mechanical energy. We show that native proteins give rise to viscoelastic behavior, while denatured proteins display poroelasticity, and, most notably, that these two regimes can reversibly switch within the same material. This discovery introduces a new concept of dynamically tunable soft materials, advancing biomaterial design beyond static systems. Our work combines mechanical testing, molecular-level insights, and machine learning-based analysis to connect protein structure with hydrogel mechanics across length scales. These findings open new pathways for designing smart biomaterials with applications in tissue engineering and related biomedical technologies.