Mechanical Causation of Biological Structure: Productive Pulls Produce Persistent Filaments in a Human Fibroblast Model of Matrix Development
Silverman, A. A.; Siadat, S. M.; Olszewski, J. D.; Ruberti, J. W.
Show abstract
The principal mechanisms driving the synthesis and organization of durable animal structure have been the subject of intense investigation for decades. Here, we present evidence that mechanical strains can direct the formation of extracellular matrix (ECM) filaments via a mechanochemical cascade. This process is driven by cooperative cell contractions ("pulls") that organize and precipitate structure via strain-induced polymer assembly. In an in vitro model of ECM synthesis, we use high-resolution optical microscopy to observe the kinematics of cell motion during their growth to confluency and identified cell-to-cell pulls that result in the production of persistent ECM filaments. Using live-cell confocal imaging, we confirmed that these pulls can directly cause the formation of fibronectin filaments that then bind collagen, producing persistent structures aligned with the direction of the pull. The finding suggests a new model for initial durable structure formation in animals based on local cell contraction, extensional strain and polymer mechanochemistry. The results have important implications for ECM development, growth and life-threatening pathologies of the ECM such as fibrosis.
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