Membrane-dependent reactions and blood coagulation

Blood coagulation is a large reaction network (in the essence, a multistep proteolytic cascade with feedbacks) in plasma that functions to locally convert blood from fluid state into a gelatinous one, and thus to stop bleeding. In addition to this hemostatic role, coagulation has also additional vital functions in immunity and angiogenesis. The two hemostatic mechanisms, platelet aggregation and blood coagulation, work side-by-side and complement each other.

In particular, all main reactions of blood plasma coagulation cascade do not occur in plasma. They proceed on the membranes of activated platelets, endotelial cells, microparticles and other surfaces available in blood. Molecular mechanisms of these two-dimensional surface-dependent reactions are very much biophysical in their nature, and are very hard to decypher from the experimental data: too many components, two-many unstable intermediates, and the general complexity of dealing with membranes on top of that. Investigation of the membran-dependend process using experiments and modelling, and elucidation of the overall regulation of the clotting network are among our priorities and the main areas of expertise.

Blood coagulation factors bound to procoagulant platelets are concentrated in their cap structures to promote clotting

Nadezhda A. Podoplelova, Anastasia N. Sveshnikova, Yana N. Kotova, Anita Eckly, Nicolas Receveur, Dmitry Yu. Nechipurenko, Sergey I. Obydennyi, Igor I. Kireev, Christian Gachet, Fazly I. Ataullakhanov, Pierre H. Mangin, Mikhail A. Panteleev

Blood 2016 :blood-2016-02-696898; doi:10.1182/blood-2016-02-696898

Hysteresis-like binding of coagulation factors x/xa to procoagulant activated platelets and phospholipids results from multistep association and membrane-dependent multimerization

Nadezhda A. Podoplelova, Anastasia N. Sveshnikova, James H. Kurasawa, Andrey G. Sarafanov, Chambost Herve, Sergey A. Vasil'ev, Irina A. Demina, Fazly I. Ataullakhanov, Alessi Marie-Christine, and Mikhail A. Panteleev. 

Biochimica et Biophysica Acta - Biomembranes, 1858(6):1216–1227, 2016

Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion.

Panteleev MA, Dashkevich NM, Ataullakhanov FI.

Thromb Res. 2015 Oct;136(4):699-711. doi: 10.1016/j.thromres.2015.07.025. Epub 2015 Jul 29. Review.

Untangling the complexity of blood coagulation network: use of computational modelling in pharmacology and diagnostics.

Shibeko AM, Panteleev MA.

Brief Bioinform. 2015 Jun 27. pii: bbv040

Platelet surface-associated activation and secretion-mediated inhibition of coagulation factor XII.

Zakharova NV, Artemenko EO, Podoplelova NA, Sveshnikova AN, Demina IA, Ataullakhanov FI, Panteleev MA.

PLoS One. 2015 Feb 17;10(2):e0116665. doi: 10.1371/journal.pone.0116665. eCollection 2015.

Kinetics and mechanisms of surface-dependent coagulation factor XII activation.

Terentyeva VA, Sveshnikova AN, Panteleev MA.

J Theor Biol. 2015 Oct 7;382:235-43. doi: 10.1016/j.jtbi.2015.07.001. Epub 2015 Jul 14

Circulating contact-pathway-activating microparticles together with factors IXa and XIa induce spontaneous clotting in plasma of hematology and cardiologic patients.

Lipets E, Vlasova O, Urnova E, Margolin O, Soloveva A, Ostapushchenko O, Andersen J, Ataullakhanov F, Panteleev M.


PLoS One. 2014 Jan 31;9(1):e87692. doi: 10.1371/journal.pone.0087692. eCollection 2014.

Factor XI and traveling waves: the key to understanding coagulation in hemophilia?

Ataullakhanov FI, Dashkevich NM, Negrier C, Panteleev MA.

Expert Rev Hematol. 2013 Apr;6(2):111-3. doi: 10.1586/ehm.13.12.

Procoagulant platelets form an α-granule protein-covered "cap" on their surface that promotes their attachment to aggregates.

Abaeva AA, Canault M, Kotova YN, Obydennyy SI, Yakimenko AO, Podoplelova NA, Kolyadko VN, Chambost H, Mazurov AV, Ataullakhanov FI, Nurden AT, Alessi MC, Panteleev MA.

J Biol Chem. 2013 Oct 11;288(41):29621-32. doi: 10.1074/jbc.M113.474163. Epub 2013 Aug 30.

Thrombin activity propagates in space during blood coagulation as an excitation wave.

Dashkevich NM, Ovanesov MV, Balandina AN, Karamzin SS, Shestakov PI, Soshitova NP, Tokarev AA, Panteleev MA, Ataullakhanov FI.

Biophys J. 2012 Nov 21;103(10):2233-40. doi: 10.1016/j.bpj.2012.10.011. Epub 2012 Nov 20.

Two types of procoagulant platelets are formed upon physiological activation and are controlled by integrin α(IIb)β(3).

Topalov NN, Yakimenko AO, Canault M, Artemenko EO, Zakharova NV, Abaeva AA, Loosveld M, Ataullakhanov FI, Nurden AT, Alessi MC, Panteleev MA.

Arterioscler Thromb Vasc Biol. 2012 Oct;32(10):2475-83. doi: 10.1161/ATVBAHA.112.253765. Epub 2012 Jul 26.

Positive feedback loops for factor V and factor VII activation supply sensitivity to local surface tissue factor density during blood coagulation.

Balandina AN, Shibeko AM, Kireev DA, Novikova AA, Shmirev II, Panteleev MA, Ataullakhanov FI.

Biophys J. 2011 Oct 19;101(8):1816-24. doi: 10.1016/j.bpj.2011.08.034.

Task-oriented modular decomposition of biological networks: trigger mechanism in blood coagulation.

Panteleev MA, Balandina AN, Lipets EN, Ovanesov MV, Ataullakhanov FI.

Biophys J. 2010 May 19;98(9):1751-61. doi: 10.1016/j.bpj.2010.01.027.

Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa.

Shibeko AM, Lobanova ES, Panteleev MA, Ataullakhanov FI.

BMC Syst Biol. 2010 Jan 26;4:5. doi: 10.1186/1752-0509-4-5.

Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets.

Sinauridze EI, Kireev DA, Popenko NY, Pichugin AV, Panteleev MA, Krymskaya OV, Ataullakhanov FI.

Thromb Haemost. 2007 Mar;97(3):425-34.

Factor VIIIa regulates substrate delivery to the intrinsic factor X-activating complex.

Panteleev MA, Ananyeva NM, Greco NJ, Ataullakhanov FI, Saenko EL.

FEBS J. 2006 Jan;273(2):374-87.

Spatial propagation and localization of blood coagulation are regulated by intrinsic and protein C pathways, respectively.

Panteleev MA, Ovanesov MV, Kireev DA, Shibeko AM, Sinauridze EI, Ananyeva NM, Butylin AA, Saenko EL, Ataullakhanov FI.

Biophys J. 2006 Mar 1;90(5):1489-500. Epub 2005 Dec 2.

Two subpopulations of thrombin-activated platelets differ in their binding of the components of the intrinsic factor X-activating complex.

Panteleev MA, Ananyeva NM, Greco NJ, Ataullakhanov FI, Saenko EL.

J Thromb Haemost. 2005 Nov;3(11):2545-53.

Kinetics of Factor X activation by the membrane-bound complex of Factor IXa and Factor VIIIa.

Panteleev MA, Saenko EL, Ananyeva NM, Ataullakhanov FI.

Biochem J. 2004 Aug 1;381(Pt 3):779-94.

Tissue factor pathway inhibitor: a possible mechanism of action.

Panteleev MA, Zarnitsina VI, Ataullakhanov FI.

Eur J Biochem. 2002 Apr;269(8):2016-31.