Viscoelastic properties of ECM differentially regulate monocyte patterns of gene expression

Myelofibrosis (MF) is a progressive, bone marrow (BM) malignancy associated with monocytosis, and is believed to promote the pathological remodelling of the extracellular matrix. Here, we show that the mechanical properties of MF, namely the liquid-to-solid properties (viscoelasticity) of BM, contribute to aberrant differentiation of monocytes. Human monocytes cultured in stiff, elastic hydrogels show pro-inflammatory polarization and differentiation towards dendritic cells, as opposed to those cultured in a viscoelastic matrix. Human primary monocytes were encapsulated in artificial fibrotic matrix hydrogels for 3 days in soft vs. stiff and viscous vs. elastic conditions to test the effects of mechanical cues on gene transcription of monocytes by a custom nanoString panel of myeloid markers