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Assessment of Fibrinogen Macromolecules Interaction with Red Blood Cells Membrane by Means of Laser Aggregometry, Flow Cytometry, and Optical Tweezers Combined with Microfluidics

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Department of Physics, M.V. Lomonosov Moscow State University, Leninskie Gory 1/2, 119991 Moscow, Russia
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International Laser Center, M.V. Lomonosov Moscow State University, Leninskie Gory 1/62, 119991 Moscow, Russia
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Institute of Spectroscopy of the Russian Academy of Sciences, Troitsk, Fizicheskaya st., 5, 108840 Moscow, Russia
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Department of Advanced Biomaterials, Institute for Regenerative Medicine, Sechenov University, 2-8 Trubetskaya St., 119991 Moscow, Russia
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Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
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Faculty of Fundamental Medicine, K.D. Ushinskiy Yaroslavl State Pedagogical University, Respublikanskaya st. 108, 150000 Yaroslavl, Russia
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Campus Building E2 6, Saarland University, Experimental Physics, D-66041 Saarbrücken, Germany
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University of Luxembourg, Physics and Materials Science Research Unit, L-1511 Luxembourg, Luxembourg
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School of Mechanical Engineering, Korea University, Seoul, Anam-dong, Seongbuk-gu 02841, Korea
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Author to whom correspondence should be addressed.
Biomolecules 2020, 10(10), 1448; https://doi.org/10.3390/biom10101448
Received: 5 September 2020 / Revised: 7 October 2020 / Accepted: 12 October 2020 / Published: 15 October 2020
(This article belongs to the Special Issue Biochemical and Biophysical Properties of Red Blood Cells in Disease)
An elevated concentration of fibrinogen in blood is a significant risk factor during many pathological diseases, as it leads to an increase in red blood cells (RBC) aggregation, resulting in hemorheological disorders. Despite the biomedical importance, the mechanisms of fibrinogen-induced RBC aggregation are still debatable. One of the discussed models is the non-specific adsorption of fibrinogen macromolecules onto the RBC membrane, leading to the cells bridging in aggregates. However, recent works point to the specific character of the interaction between fibrinogen and the RBC membrane. Fibrinogen is the major physiological ligand of glycoproteins receptors IIbIIIa (GPIIbIIIa or αIIββ3 or CD41/CD61). Inhibitors of GPIIbIIIa are widely used in clinics for the treatment of various cardiovascular diseases as antiplatelets agents preventing the platelets’ aggregation. However, the effects of GPIIbIIIa inhibition on RBC aggregation are not sufficiently well studied. The objective of the present work was the complex multimodal in vitro study of the interaction between fibrinogen and the RBC membrane, revealing the role of GPIIbIIIa in the specificity of binding of fibrinogen by the RBC membrane and its involvement in the cells’ aggregation process. We demonstrate that GPIIbIIIa inhibition leads to a significant decrease in the adsorption of fibrinogen macromolecules onto the membrane, resulting in the reduction of RBC aggregation. We show that the mechanisms underlying these effects are governed by a decrease in the bridging components of RBC aggregation forces. View Full-Text
Keywords: fibrinogen macromolecules; RBC membrane; optical (laser) tweezers; flow cytometry; glycoproteins IIbIIIa inhibition; microfluidics fibrinogen macromolecules; RBC membrane; optical (laser) tweezers; flow cytometry; glycoproteins IIbIIIa inhibition; microfluidics
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Semenov, A.N.; Lugovtsov, A.E.; Shirshin, E.A.; Yakimov, B.P.; Ermolinskiy, P.B.; Bikmulina, P.Y.; Kudryavtsev, D.S.; Timashev, P.S.; Muravyov, A.V.; Wagner, C.; Shin, S.; Priezzhev, A.V. Assessment of Fibrinogen Macromolecules Interaction with Red Blood Cells Membrane by Means of Laser Aggregometry, Flow Cytometry, and Optical Tweezers Combined with Microfluidics. Biomolecules 2020, 10, 1448.

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