Long-range mechanical coupling of cells in 3D fibrin gels

Sari Natan, Yoni Koren, Ortal Shelah, Shahar Goren, Ayelet Lesman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

When seeded in fibrous gels, pairs of cells or cell aggregates can induce bands of deformed gel, extending to surprisingly long distances in the intercellular medium. The formation of bands has been previously shown and studied in collagen systems. In this study, we strive to further our understanding of this fundamental mechanical mechanism in fibrin, a key element in wound healing and angiogenesis processes. We embedded fibroblast cells in 3D fibrin gels, and monitored band formation by real-time confocal microscopy. Quantitative dynamic analysis of band formation revealed a gradual increase in fiber density and alignment between pairs of cells. Such intercellular bands extended into a large-scale network of mechanically connected cells, in which the connected cells exhibited a more spread morphology than the isolated cells. Moreover, computational modeling demonstrated that the direction of cell-induced force triggering band formation can be applied in a wide range of angles relative to a neighboring cell. Our findings indicate that long-range mechanical coupling between cells is an important mechanism in regulating multicellular processes in reconstituted fibrin gels. As such, it should motivate exploration of this mechanism in studies in vivo, in wound healing or angiogenesis, in which fibrin is contracted by fibroblast cells.

Original languageEnglish
Pages (from-to)1474-1485
Number of pages12
JournalMolecular Biology of the Cell
Volume31
Issue number14
DOIs
StatePublished - 1 Jul 2020

Funding

FundersFunder number
Israel Science Foundation - Israeli Centers for Research Excellence1902/12
Zimin Institute for Engineering Solutions Advancing Better Lives
Israel Science Foundation1474/16

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