Winding-Up of Fibrin Fibers as a Novel Mechanism of Platelet-Mediated Fiber Compaction

Abstract

This study reveals a previously unrecognized mechanism by which platelets retract and compact fibrin fibers. Using a newly developed 2D fiber-retraction assay, we observed an initial "gearwheel" pattern of actin-myosin organization in spread platelets with associated, extracellular fibrin patches that appear to form an initiation complex for fibrin fiber attachment and rearrangement. The final outcome of this process results in two morphologically different platelet populations. Spread platelets with coiled fibers around and above their pseudo-nucleus. Other platelets are only partially spread on the glass surface and are surrounded by tightly packed fibrin fibers around bulbous protrusions ("bulbs"), mirroring the architecture of platelets and adjacent fibers within a retracted clot. Thus, the observed compaction process might also take place during clot retraction in order to reduce clot volume, stiffen the clot and enhance wound repair. Apart from pulling on fibers like on a rope, platelets actively wrap fibrin fibers into compact structures, similar to balls of wool. Besides DNA packaging, this represents a new example of a natural fiber compaction mechanism. Using a combination of 3D clot-retraction and 2D fiber-retraction assays, expansion and electron microscopy, live imaging and mathematical modeling, we show that platelets use an actomyosin-driven motion to gather and loop fibrin fibers around the base of bulbous protrusions. These bulbs form when a platelet becomes trapped between fibrin fibers during 3D clot retraction or 2D fiber-retraction assays. These findings complement and extend earlier models of platelet-mediated fibrin fiber retractions, offering new insight into how platelets mechanically organize fibrin fibers.