Early Stages in Clot Formation — an unexpected role for bubbles (2013)

Undergraduates: Adam Turner, Michael R. Falvo, Richard Superfine

Faculty Advisor: Tim O'Brien
Department: Biology

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Fibrin fiber networks are the major structural framework of blood clots, but the earliest stages of formation of clots have not been fully visualized. Understanding how blood clots actually form will allow us to develop control strategies for prevention of strokes, heart attacks, and thromboses. Current theory of clot formation describes an endwise stochastic growth of a growing fiber, but this view has serious drawbacks. By starting the polymerization process on plasma cleaned optical cover glass made hydrophobic with hexamethyldisilazane, rapidly fixing the reaction at very early stages (5-30 sec) with glutaraldehyde, and carefully dehydrating and critical point drying each sample, we were able to image what we think are the pre-fiber stages of clot formation. We compared preparations of pure fibrinogen, and pooled human plasma to fixed human clots. We imaged each sample using ultra-high resolution SEM imaging, capable of imaging in the range of single monomers. We find that the first forms of polymers are large sheets, and small bubbles. These apparently inflate and coalesce into a foam, that then condenses into fibers. This finding is a new way of thinking about fibrin polymerization, which promises new avenues for understanding and possibly controlling clot formation in vivo and possibly in industrial settings.