Gradual Stress‐Relaxation of Hydrogel Regulates Cell Spreading

Abstract

There is growing evidence that the mechanical properties of extracellular matrices (ECMs), including elasticity and stress‐relaxation, greatly influence the function and form of the residing cells. However, the effects of elasticity and stress‐relaxation are often correlated, making the study of the effect of stress‐relaxation on cellular behaviors difficult. Here, we designed a hybrid network hydrogel with a controllable stress‐relaxation gradient and a constant elasticity. The hydrogel is crosslinked by covalent bonds and dynamic peptide‐metal ion coordination interactions. The stress‐relaxation gradient is controlled by spatially controlling the coordination and covalent crosslinker ratios. The different parts of the hydrogel exhibit distinct stress‐relaxation amplitudes but the have same stress‐relaxation timescale. Based on this hydrogel, we investigate the influence of hydrogel stress‐relaxation on cell spreading. Our results show that the spreading of cells is suppressed at an increasing stress‐relaxation amplitude with a fixed elasticity and stress‐relaxation timescale. Our study provides a universal route to tune the stress‐relaxation of hydrogels without changing their components and elasticity, which may be valuable for systematic investigations of the stress‐relaxation gradient in cell cultures and organoid constructions.