Abstract

The mechanical properties of extracellular matrices can control the function of cells. Studies of cellular responses to biomimetic soft materials have been largely restricted to hydrogels and elastomers that have stiffness values independent of time and extent of deformation, so the substrate stiffness can be unambiguously related to its effect on cells. Real tissues, however, often have loss moduli that are 10 to 20% of their elastic moduli and behave as viscoelastic solids. The response of cells to a time-dependent viscous loss is largely uncharacterized because appropriate viscoelastic materials are lacking for quantitative studies. Here we report the synthesis of soft viscoelastic solids in which the elastic and viscous moduli can be independently tuned to produce gels with viscoelastic properties that closely resemble those of soft tissues. Systematic alteration of the hydrogel viscosity demonstrates the time dependence of cellular mechanosensing and the influence of viscous dissipation on cell phenotype.

Highlights

  • The mechanical properties of extracellular matrices can control the function of cells

  • We report the synthesis of soft viscoelastic solids for which the elastic and viscous moduli can be independently tuned to produce gels with viscoelastic properties that mimic those of soft tissues

  • Our PAA gels differ in this respect from the system reported by Cameron et al.[19]; their partially crosslinked PAA gels keep flowing under the application of a constant stress, which is typical of viscoelastic fluids

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Summary

Introduction

The mechanical properties of extracellular matrices can control the function of cells. Most studies of cellular mechanosensing have used purely elastic crosslinked polyacrylamide gels[1,2] with almost no dissipation of deformation energy (loss modulus) Real tissues such as brain, liver, spinal cord and fat often have loss moduli that are 10 to 20% of their elastic storage moduli[3,4,5,6,7,8] over a large range of time scales. We report the synthesis of soft viscoelastic solids for which the elastic and viscous moduli can be independently tuned to produce gels with viscoelastic properties that mimic those of soft tissues This was done by creating permanently crosslinked networks of polyacrylamide (PAA) that sterically entrap but do not bind very high molecular weight linear polymers of PAA. The chemistry of these systems allows cell adhesion ligands such as collagen and fibronectin to be attached exclusively to the crosslinked elastic network, to the viscous linear chains or to both viscous and elastic elements

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