Local-friction governs water mobility in hydrogels acting as extracellular mimics

Abstract

The extracellular matrix (ECM) controls essential cellular processes, including migration, proliferation, and regeneration. Recent counterintuitive studies demonstrate improved cell motility in hyper-viscous settings, raising basic questions about the functionality of the extracellular matrix (ECM) despite the usual expectation that a uniform-viscous ECM is ideal for its function. In this study, we propose that “local friction or micro-viscosity” – rather than bulk viscosity – more accurately governs molecular dynamics within ECM-like environments. Building on our previous findings, in which nanoparticle-embedded chitosan hydrogels showed scar-free wound healing, we have investigated the water dynamic behaviour across varying viscosities using a methylcellulose solution (mimicking cell viscosity) and pH-dependent chitosan hydrogels. By employing dielectric relaxation and ultrafast solvation spectroscopy, we characterize distinct water populations, namely free water, loosely bound water (biological water), and structurally ordered water inside the ECM matrix, and highlight their independent contributions related to the micro-viscosity. Our results suggest that the relative abundance and dynamics of these water types are related to viscoelasticity, which underlie the exceptional therapeutic behaviour of ECM-mimetic materials, offering a new paradigm for understanding cellular microenvironments. This work advances the concept of “functional water dynamics” as a complementary mechanism in cell–matrix interaction models.