Fibrin gels as a novel model for examining collagen organization by cardiac fibroblasts

The collagen network within the heart, produced by cardiac fibroblasts, provides a structural framework and transmits mechanical information during contraction. Synthesis and organization of collagen increases during neonatal development as the heart adapts to increased hemodynamic load. How fibroblasts organize collagen within the heart is unknown. A three‐dimensional fibrin gel model was used to begin to elucidate the mechanisms whereby fibroblasts organize the collagenous matrix. Fibrin gels containing neonatal fibroblasts were fixed after 24–72 hours in culture and examined by confocal microscopy to determine the distribution of fibroblasts, localization of discoidin domain receptor 2 (DDR2) and collagen. Collagen synthesis, measured at both protein and RNA levels, increased indicating that cardiac fibroblasts were laying down new collagen matrix. No significant changes in MMP2 activity in conditioned media were observed. Confocal microscopy revealed that fibroblasts were randomly distributed throughout the fibrin gels and the type I collagen distribution paralleled that of the fibroblasts and overlapped somewhat with the expression of DDR2 on the fibroblast cell surface. These studies demonstrate that fibrin gels are an excellent model system in which to examine collagen organization by cardiac fibroblasts. This work was supported by NIH grant HL73937.