Exploring pH-Responsive, Switchable Crosslinking Mechanisms for Programming Reconfigurable Hydrogels Based on Aminopolysaccharides

Dynamic, stimuli-responsive, reconfigurable materials are finding growing interest and applications. A recent experiment (He et al., Adv Funct Matter., 2017) demonstrated a pH-responsive, reconfigurable hydrogel film based on a single biopolymer chitosan and two physical cross-linking mechanisms. Here, we use state-of-the-art molecular dynamics simulations to gain atomically detailed insights into the three salient features of this experimental system: (1) a pH-responsive switch between the crystalline network junctions formed by intermolecular hydrogen bonding between chitosan chains and electrostatic cross-links based on sodium dodecyl sulfate (SDS) micelles; (2) viscoelastic behavior of the SDS-crosslinked network; and (3) a stable but erasable gradient between the two cross-linked regions. Our simulations showed that the electrostatic cross-links are formed through the pH-dependent salt-bridge interactions between the chitosan glucosamines and SDS sulfates. Interestingly, the strength and directionality of the salt-bridge interactions give rise to complementary shape changes, despite the intrinsic stiffness of the chitosan chain or the hydrophobic forces that keep the micelle intact. Additionally, the salt-bridge contacts display temporal and spatial dynamics, which offers a microscopic explanation of the viscoelastic properties of the SDS-crosslinked network. Another significant finding is the pKa difference between the chitosan crystallite and the SDS-bound chitosan chain, which provides a physical origin for the persistent but erasable gradient in the structural and mechanical properties between the two cross-linked regions. pKa gradients are integral to protein structures and functions; our finding suggested that they may be important for polysaccharides and broadly exploited for designing pH-responsive, reconfigurable, complex, multifunctional materials. Our work provides a glimpse at how modern computer simulations can advance the understanding and potentially guide the design of novel soft matter.