Modeling collagen fibril self-assembly from extracellular medium in embryonic tendon

Christopher K. Revell, Jeremy A. Herrera, Craig Lawless, Yinhui Lu, Karl E. Kadler, Joan Chang, Oliver E. Jensen

Research output: Contribution to journalArticlepeer-review


Collagen is a key structural component of multicellular organisms and is arranged in a highly organized manner. In structural tissues such as tendons, collagen forms bundles of parallel fibers between cells, which appear within a 24-h window between embryonic day 13.5 (E13.5) and E14.5 during mouse embryonic development. Current models assume that the organized structure of collagen requires direct cellular control, whereby cells actively lay down collagen fibrils from cell surfaces. However, such models appear incompatible with the time and length scales of fibril formation. We propose a phase-transition model to account for the rapid development of ordered fibrils in embryonic tendon, reducing reliance on active cellular processes. We develop phase-field crystal simulations of collagen fibrillogenesis in domains derived from electron micrographs of inter-cellular spaces in embryonic tendon and compare results qualitatively and quantitatively to observed patterns of fibril formation. To test the prediction of this phase-transition model that free protomeric collagen should exist in the inter-cellular spaces before the formation of observable fibrils, we use laser-capture microdissection, coupled with mass spectrometry, which demonstrates steadily increasing free collagen in inter-cellular spaces up to E13.5, followed by a rapid reduction of free collagen that coincides with the appearance of less-soluble collagen fibrils. The model and measurements together provide evidence for extracellular self-assembly of collagen fibrils in embryonic mouse tendon, supporting an additional mechanism for rapid collagen fibril formation during embryonic development.

Original languageEnglish
Pages (from-to)3219-3237
Number of pages19
Issue number16
Publication statusPublished - 22 Aug 2023


Dive into the research topics of 'Modeling collagen fibril self-assembly from extracellular medium in embryonic tendon'. Together they form a unique fingerprint.

Cite this