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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.

SUBMITTER: Yu W

PROVIDER: S-EPMC9100461 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Gradual Stress-Relaxation of Hydrogel Regulates Cell Spreading.

Yu Wenting W Sun Wenxu W Chen Huiyan H Wang Juan J Xue Bin B Cao Yi Y

International journal of molecular sciences 20220505 9

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 cros ...[more]

PMID: 35563561

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Project description:Mechanical properties of the extracellular microenvironment are known to alter cellular behavior, such as spreading, proliferation or differentiation. Previous studies have primarily focused on studying the effect of matrix stiffness on cells using hydrogel substrates that exhibit purely elastic behavior. However, these studies have neglected a key property exhibited by the extracellular matrix (ECM) and various tissues; viscoelasticity and subsequent stress-relaxation. As muscle exhibits viscoelasticity, stress-relaxation could regulate myoblast behavior such as spreading and proliferation, but this has not been previously studied. In order to test the impact of stress relaxation on myoblasts, we created a set of two-dimensional RGD-modified alginate hydrogel substrates with varying initial elastic moduli and rates of relaxation. The spreading of myoblasts cultured on soft stress-relaxing substrates was found to be greater than cells on purely elastic substrates of the same initial elastic modulus. Additionally, the proliferation of myoblasts was greater on hydrogels that exhibited stress-relaxation, as compared to cells on elastic hydrogels of the same modulus. These findings highlight stress-relaxation as an important mechanical property in the design of a biomaterial system for the culture of myoblasts.Statement of significanceThis article investigates the effect of matrix stress-relaxation on spreading and proliferation of myoblasts by using tunable elastic and stress-relaxing alginate hydrogels substrates with different initial elastic moduli. Many past studies investigating the effect of mechanical properties on cell fate have neglected the viscoelastic behavior of extracellular matrices and various tissues and used hydrogels exhibiting purely elastic behavior. Muscle tissue is viscoelastic and exhibits stress-relaxation. Therefore, stress-relaxation could regulate myoblast behavior if it were to be incorporated into the design of hydrogel substrates. Altogether, we showed that stress-relaxation impacts myoblasts spreading and proliferation. These findings enable a better understanding of myoblast behavior on viscoelastic substrates and could lead to the design of more suitable substrates for myoblast expansion in vitro.

Dataset Information

Gradual Stress-Relaxation of Hydrogel Regulates Cell Spreading.

Publications

Gradual Stress-Relaxation of Hydrogel Regulates Cell Spreading.

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