title: Fibers in the extracellular matrix enable long-range stress transmission between cells.
abstract: 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.
authors.affiliation: The Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Ma
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Schickel
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stevenson
authors.forename: Alisha L
authors.initials: AL
authors.lastname: Sarang-Sieminski
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Gooch
authors.forename: Samir N
authors.initials: SN
authors.lastname: Ghadiali
authors.forename: Richard T
authors.initials: RT
authors.lastname: Hart
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D020342:Finite Element Analysis; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D013314:Stress, Mechanical
chemical_list: D003094:Collagen
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