Kalashnikov Nikita, Moraes Christopher
Department of Chemical Engineering, McGill University, Montreal, Canada.
Department of Biological and Biomedical Engineering, McGill University, Montreal, Canada.
Soft Matter. 2023 Mar 29;19(13):2438-2445. doi: 10.1039/d2sm01683d.
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.
粘弹性是许多活组织的固有特性，为了在细胞培养中更好地重现这一特性，人们设计了水凝胶生物材料，使其表现出随时间变化的能量耗散力学行为。粘弹性水凝胶培养平台有助于理解粘弹性的生物学效应。尽管已经证明粘弹性可调节诸如贴壁细胞的铺展和分化等基本细胞过程，但尚未探讨粘弹性对巨噬细胞行为的影响。在此，我们使用可调谐的粘弹性聚丙烯酰胺水凝胶培养系统来证明粘弹性是巨噬细胞功能的重要生物物理调节因子。在用HS-5成纤维细胞对我们的系统进行生物学验证以显示与现有报告一致的行为后，我们将人THP-1单核细胞接种在这些粘弹性底物上并将它们分化为巨噬细胞。THP-1巨噬细胞在更粘稠的聚丙烯酰胺水凝胶底物上变得更小、更圆，并且吞噬作用效率更低。由于巨噬细胞在诸如炎症和纤维化等反应中起关键作用，这些结果表明粘弹性是免疫调节生物材料设计中的一个重要参数。
