Significance
Cellular mechanosensing of fibrillar extracellular matrices plays a critical role in homeostasis and disease progression in stromal connective tissue. Here, we established a new material system composed of electrospun dextran vinyl sulfone polymeric fibers. These matrices exhibit architectural, mechanical, and biochemical tunability to accurately model diverse tissue microenvironments found in the body. In contrast to previous observations with non-fibrous hydrogels, we find that fibroblasts in soft and deformable fibrous matrices exhibit increased spreading and focal adhesion formation as compared to those in stiffer matrices with equivalent architecture. We also investigated the role of matrix stiffness on myofibroblast activation, a critical step in the fibrotic cascade, and find that low stiffness matrices promote increased myofibroblast activation.
Statement of significance
Cellular mechanosensing of fibrillar extracellular matrices plays a critical role in homeostasis and disease progression in stromal connective tissue. Here, we established a new material system composed of electrospun dextran vinyl sulfone polymeric fibers. These matrices exhibit architectural, mechanical, and biochemical tunability to accurately model diverse tissue microenvironments found in the body. In contrast to previous observations with non-fibrous hydrogels, we find that fibroblasts in soft and deformable fibrous matrices exhibit increased spreading and focal adhesion formation as compared to those in stiffer matrices with equivalent architecture. We also investigated the role of matrix stiffness on myofibroblast activation, a critical step in the fibrotic cascade, and find that low stiffness matrices promote increased myofibroblast activation.