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Abstract
Red blood cells (RBCs) are a major component of blood clots, which form physiologically
as a response to injury or pathologically in thrombosis. The active participation
of RBCs in thrombus solidification has been previously proposed but not yet experimentally
proven. Holographic optical tweezers and single-cell force spectroscopy were used
to study potential cell-cell adhesion between RBCs. Irreversible intercellular adhesion
of RBCs could be induced by stimulation with lysophosphatidic acid (LPA), a compound
known to be released by activated platelets. We identified Ca2+ as an essential player
in the signaling cascade by directly inducing Ca2+ influx using A23187. Elevation
of the internal Ca2+ concentration leads to an intercellular adhesion of RBCs similar
to that induced by LPA stimulation. Using single-cell force spectroscopy, the adhesion
of the RBCs was identified to be approximately 100 pN, a value large enough to be
of significance inside a blood clot or in pathological situations like the vasco-occlusive
crisis in sickle cell disease patients.