Cells can sense, signal and organize via mechanical forces. The ability of cells to mechanically sense and respond to the presence of other cells over relatively long distances across extracellular matrix (ECM) has been attributed to the strain-hardening behavior of the ECM. In this study, we explore an alternative hypothesis that the fibrous nature of the ECM makes long-range stress transmission possible, which could provide a mechanism for long-range cell-cell mechanical signaling. To test this hypothesis, we built 2-D and 3-D finite element models of stress transmission within cell-seeded collagen gels. To examine the role of collagen fibers in lateral stress transmission, confocal reflectance microscopy was used to develop 2-D image-based finite-element models. Models that account for the gel’s fibrous nature were compared with homogenous linearelastic and strain-hardening models to investigate the mechanisms of stress propagation. To examine the role of collagen fibers in cell thickness sensing, 3-D finite element models with idealized fiber networks were built, and the stress transmissions in fibrous and homogeneous ECM were compared. Finite-element analysis revealed that stresses generated by cell contraction are concentrated in the relatively stiff ECM fibers and are propagated farther in a fibrous matrix as compared to linear elastic or strain-hardening homogenous materials. These results support the hypothesis that ECM fibers, especially aligned ones, play an important role in long-range stress transmission. Further, fluid-structure interaction models were built to investigate the interplay between collagen fibers and interstitial fluid. The results suggest that in cell culture, cell movement is the key factor in defining fluid-flow development at the microscopic ‘cellular’ level, and the cross-links are the key factor that determines the micro-mechanical environment.