Red Blood Cells Take on Many-Sided Shape During Clotting

Posted: Published on January 10th, 2014

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Newswise PHILADELPHIA - Red blood cells are the bodys true shape shifters, perhaps the most malleable of all cell types, transforming among many other forms -- into compressed discs capable of going through capillaries with diameters smaller than the blood cell itself. While studying how blood clots contract John W. Weisel, Ph.D., professor of Cell and Developmental Biology at the Perelman School of Medicine, University of Pennsylvania, and colleagues, discovered a new geometry that red blood cells assume, when compressed during clot formation.

Although red blood cells were first visualized in the mid-17th century and studied extensively since then, this new study, published online ahead of print in the journal Blood, describes a previously unknown shape and potential new function for red blood cells. The Penn team found that red blood cells can be compressed into many-sided, closely-packed polyhedral structures instead of their free-flowing bi-concave, disc shape.

Whats more, contrary to expectations, the aggregates of fibrin and platelets that make up highly contracted clots lie primarily on the clot exterior, with the red blood cells crowded within the clot interior, although the contents of clots are more homogeneous before contraction takes place.

Contracted clots may form an impermeable seal and help prevent vascular obstruction, but confer resistance to penetration by drugs that break down fibrin, the structural component of clots, a common treatment option for heart attacks and strokes.

The first time we saw this, we thought: This cant be biological, recalls Weisel. The team first saw the polyhedron-shaped red blood cells when studying the clot-contraction process using a novel magnetic resonance technology, with co-authors from T2 Biosystems, along with co-author Douglas Cines, M.D., director of the Coagulation Laboratory and professor of Pathology and Laboratory Medicine at Penn. They observed a signal that indicated tightly packed red blood cells.

The Clot Network Clots are a three-dimensional network of fibers, made up primarily of the blood protein fibrinogen, which is converted to fibrin during clotting, and platelets, which aggregate by binding to fibrin once they are activated. A blood clot needs to have the right degree of stiffness and plasticity to stem the flow of blood when tissue is damaged, yet be flexible enough that it does not block blood flow.

After a clot forms, the actin and myosin in platelets start the contraction process and cause the clot to shrink to about one-third of its original size. This is an important step to stem bleeding, to decrease obstruction in blood vessels, and to provide a matrix for migration of cells involved in wound healing. Red blood cells are caught up in the contraction process, especially in the venous system, and get pulled by the platelets towards the interior of the clot, as the Blood study indicates.

Little was known about the structure of contracted clots or the role of red blood cells in the contraction process. We found that contracted blood clots develop a remarkable structure, with a meshwork of fibrin and platelet aggregates on the exterior of the clot and a close-packed, tessellated array of compressed polyhedral erythrocytes within, says Weisel.

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Red Blood Cells Take on Many-Sided Shape During Clotting

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