Fibers in the Extracellular Matrix Enable Long-Range Stress Transmission between Cells

• Published in: Biophysical journal Vol. 104; no. 7; pp. 1410 - 1418
• Main Authors: Ma, Xiaoyue, Schickel, Maureen E., Stevenson, Mark D., Sarang-Sieminski, Alisha L., Gooch, Keith J., Ghadiali, Samir N., Hart, Richard T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.04.2013; Biophysical Society; The Biophysical Society
• Subjects: Animals; Biomechanical Phenomena; Biophysics; Cell Biophysics; Cells; collagen; Collagen - metabolism; extracellular matrix; Extracellular Matrix - metabolism; Fibers; Finite Element Analysis; gels; Mice; microscopy; Microscopy, Confocal; NIH 3T3 Cells; reflectance; Signal transduction; Strain hardening; Stress analysis; Stress, Mechanical
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2013.02.017

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 (e.g., ∼100 μm, or ∼10 cell-diameters) across extracellular matrix (ECM) has been attributed to the strain-hardening behavior of the ECM. In this study, we explore an alternative hypothesis: the fibrous nature of the ECM makes long-range stress transmission possible and provides an important mechanism for long-range cell-cell mechanical signaling. To test this hypothesis, confocal reflectance microscopy was used to develop image-based finite-element models of stress transmission within fibroblast-seeded collagen gels. Models that account for the gel’s fibrous nature were compared with homogenous linear-elastic and strain-hardening models to investigate the mechanisms of stress propagation. Experimentally, cells were observed to compact the collagen gel and align collagen fibers between neighboring cells within 24 h. Finite-element analysis revealed that stresses generated by a centripetally contracting cell boundary are concentrated in the relatively stiff ECM fibers and are propagated farther in a fibrous matrix as compared to homogeneous linear elastic or strain-hardening materials. These results support the hypothesis that ECM fibers, especially aligned ones, play an important role in long-range stress transmission.