Abstract
Alterations in the adipose tissue extracellular matrix are well established in obesity, but the role of matrix mechanics in regulating adipocyte function is not well understood. We used a hydrogel-adipocyte culture system to study the effects of matrix stiffness on adipocyte function. We found that intermediate matrix stiffness approximating native human adipose tissue promoted maximal adipogenesis and lipid storage, while stiffness above or below this threshold impaired adipogenesis and lipid storage. Transcriptomic analysis revealed that matrix stiffness regulated diverse signaling pathways in adipocytes related to lipid metabolism, immunity and inflammation, angiogenesis, and extracellular matrix interactions. These data elucidate the role of matrix mechanics in regulating adipocyte function and will guide further studies towards developing optimal matrix characteristics for adipocytes in in vitro culture models and designing adipocyte delivery vehicles for in vivo translational applications.