Ruberti Lab Shows That Collagen Deposition by Fibroblasts Producing Organized Corneal Tissue is Guided by Dynamic Tension

Tension in the ranks: Cooperative cell contractions drive force-dependent collagen assembly in human fibroblast culture

Matter

SUMMARY

Currently, there is no mechanistic model that fully explains the initial synthesis and organization of durable animal structure. As a result, our understanding of extracellular matrix (ECM) development and pathologies (e.g., persistent fibrosis) remains limited. Here, we identify and characterize cell-generated mechanical strains that direct the assembly of the ECM. Cell kinematics comprise cooperative retrograde “pulls” that organize and precipitate biopolymer structure along lines of tension. High-resolution optical microscopy revealed five unique classes of retrograde “pulls” that result in the production of filaments. Live-cell confocal imaging confirmed that retrograde pulls can directly cause the formation of fibronectin filaments that then colocalize with collagen aggregates exported from the cell, producing persistent elongated structures aligned with the direction of the tension. The findings suggest a new model for initial durable structure formation in animals. The results have important implications for ECM development and growth and life-threatening pathologies of the ECM, such as fibrosis.