Losing the split ends: unraveling the mechanisms of fiber branching during blood clot formation
Abstract
The coagulation cascade generates a three-dimensional fibrin gel that seals wounds and prevents the loss of blood. Extensive research has defined the structural and mechanical characteristics of fibrin gels and the various biochemical, physiological, and pathological factors that alter those properties. However, there has been no direct visualization of fibrin polymerization with the spatial and temporal resolution to characterize the fibrin branching process. Thus, a mechanistic explanation for the origins of fibrin structures remains unresolved, with several hypothesized models for how fibrin branching occurs. Using SimView light-sheet microscopy, we captured videos of fibrin fibers forming junctions and gelling. Results: We observed four distinct pathways for fibrin fibers to interact and bind, all predicated on the observation that tumbling and diffusing fibers collide and stick together. Branching occurred due to the binding of mature fibers, not through the splitting of fibers or through the lateral association of small fibrin oligomers (protofibrils), as had been previously hypothesized. Diffusion simulations of rod-like fibers confirmed the branching mechanisms, the relative frequency of the various binding pathways, and the distribution of fiber angles after binding. Scanning Electron Microscopy (SEM) imaging also corroborated the relative frequency of various types of fibrin junctions. Moreover, SEM enabled the visualization of junctions at different timepoints, demonstrating that additional fibrin strands adhere to the initial binding site, strengthening the interaction. These results establish a mechanistic framework for fibrin branching and gel formation and define an innovative experimental approach for future interrogations of fibrin polymerization.
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BibTeX
@misc{elangovan2026losing,
title = {{Losing the split ends: unraveling the mechanisms of fiber branching during blood clot formation}},
author = {Aravind Elangovan and Dylan M. Miller and Can Cai and Key Crosley and Heather A. Belcher and Rachel M. Lee and Chad M. Hobson and David M. Hart and Martin Guthold and Brittany E. Bannish and Nathan E. Hudson},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758846},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758846v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Losing the split ends: unraveling the mechanisms of fiber branching during blood clot formation
AU - Aravind Elangovan
AU - Dylan M. Miller
AU - Can Cai
AU - Key Crosley
AU - Heather A. Belcher
AU - Rachel M. Lee
AU - Chad M. Hobson
AU - David M. Hart
AU - Martin Guthold
AU - Brittany E. Bannish
AU - Nathan E. Hudson
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758846
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758846v1
AB - The coagulation cascade generates a three-dimensional fibrin gel that seals wounds and prevents the loss of blood. Extensive research has defined the structural and mechanical characteristics of fibrin gels and the various biochemical, physiological, and pathological factors that alter those properties. However, there has been no direct visualization of fibrin polymerization with the spatial and temporal resolution to characterize the fibrin branching process. Thus, a mechanistic explanation for the origins of fibrin structures remains unresolved, with several hypothesized models for how fibrin branching occurs. Using SimView light-sheet microscopy, we captured videos of fibrin fibers forming junctions and gelling. Results: We observed four distinct pathways for fibrin fibers to interact and bind, all predicated on the observation that tumbling and diffusing fibers collide and stick together. Branching occurred due to the binding of mature fibers, not through the splitting of fibers or through the lateral association of small fibrin oligomers (protofibrils), as had been previously hypothesized. Diffusion simulations of rod-like fibers confirmed the branching mechanisms, the relative frequency of the various binding pathways, and the distribution of fiber angles after binding. Scanning Electron Microscopy (SEM) imaging also corroborated the relative frequency of various types of fibrin junctions. Moreover, SEM enabled the visualization of junctions at different timepoints, demonstrating that additional fibrin strands adhere to the initial binding site, strengthening the interaction. These results establish a mechanistic framework for fibrin branching and gel formation and define an innovative experimental approach for future interrogations of fibrin polymerization.
SN - 2692-8205
ER -