Hydrodynamic modulation of the CD44-hyaluronic acid interface via Zn2+-coordinated hyaluronic acid ligands for enhanced carbon quantum dot anisotropy

Abstract

While transition-metal-doped quantum dots exhibit enhanced anisotropy contrast, the governing interfacial thermodynamics and hydrodynamic drag remain unquantified, particularly for polarization-gated imaging. This study utilized classical molecular docking and explicit-solvent molecular dynamics (MD) to investigate the electrostatic and structural modulation of the hyaluronan-CD44 receptor interface upon the introduction of Zn²⁺ ions. Thermodynamic analysis revealed that metal coordination transitions the system into a highly specific, thermodynamically stable binding macrostate. Spatial analysis demonstrated that polymer steric constraints prevent direct inner-sphere coordination; instead, a solvent-mediated outer-sphere geometry (4.7−5.9 Å) was established, in which Zn²⁺ acts as a localized electrostatic anchor rather than as a rigid molecular cross-linker. With the disruption of the native interfacial salt-bridge network, a steric void was generated,  which allowed for the establishment of a rigid hydration shell, physically expanding the effective hydrodynamic volume (V_h) of the complex. Stokes-Einstein-Debye calculations confirmed that this solvent-swollen interface induces profound frictional drag, decelerating the theoretical rotational correlation time (θ) by 119% from 3.12 ns to 6.85 ns. This hydrodynamic shift mathematically aligns the nanoprobe's rotational tumbling with its fluorescence lifetime, proving that a solvent-mediated "hydrated ballast," rather than rigid cross-linking, is the fundamental physical driver of high-contrast anisotropy imaging.