Substrate viscoelasticity affects human macrophage morphology and phagocytosis

Viscoelasticity is an inherent characteristic of many living tissues and, in an attempt to better recapitulate this aspect in cell culture, hydrogel biomaterials have been engineered to exhibit time-dependent energy-dissipative mechanical behavior. Viscoelastic hydrogel culture platforms have been instrumental in understanding the biological effects of viscoelasticity. Although viscoelasticity has been shown to regulate fundamental cell processes such as spreading and differentiation in adherent cells, the influence of viscoelasticity on macrophage behavior has not been explored. Here, we use a tunable viscoelastic polyacrylamide hydrogel culture system to demonstrate that viscoelasticity is an important biophysical regulator of macrophage function. After biologically validating our system with HS-5 fibroblasts to show behavior consistent with existing reports, we seed human THP-1 monocytes on these viscoelastic substrates and differentiate them into macrophages. THP-1 macrophages become smaller and rounder, and less efficient at phagocytosis on more viscous polyacrylamide hydrogel substrates. Since macrophages play key roles in mounting responses such as inflammation and fibrosis, these results indicate that viscoelasticity is an important parameter in the design of immunomodulatory biomaterials.