The stiffness of the
extracellular matrix can profoundly influence cell and tissue behaviors. Thus there is an emerging emphasis on understanding how matrix mechanical environments are established, regulated, and modified. Here we develop a microrheometric
assay to measure the mechanical properties of a model
extracellular matrix (
type I collagen gel) and use it to explore cytokine-induced,
cell-mediated changes in matrix mechanical properties. The microrheometric
assay uses micron-scale ferrimagnetic
beads embedded within
collagen gels during
fibrillogenesis. The
beads are magnetized, then subjected to a twisting field, with the aggregate rotation of the
beads measured by a
magnetometer. The degree of
bead rotation reflects the stiffness of the surrounding matrix. We show that the microscale
assay provides stiffness measures for
collagen gels comparable to those obtained with standard macroscale
rheometry. To demonstrate the
utility of the
assay for biological discovery, we measure stiffness changes in fibroblast-populated
collagen gels exposed to three concentrations of six
cytokines over 2 to 14 days. Among the
cytokines tested, transforming growth factor-beta1 and interleukin-1beta enhanced matrix stiffness, and together exerted cooperative effects on cellular modulation of matrix mechanics. The microrheometry approach developed here should accelerate the discovery of biological pathways orchestrating cellular modulation of matrix mechanics.
