Platelets are small anucleated blood cells responsible for stopping bleeding. They detect blood vessel damage and agglutinate, creating aggregates and stopping the blood loss. This process is called hemostasis (from the Greek “haimatos” — blood, “stasis” — stop). Platelets become able to aggregate and plug the wound upon activation. Scientists consider that the platelet is one of the simplest cells in the human body, because the goal of its life is to decide whether activate or not. But despite this relative simplicity, numerous questions remain about the mechanisms of its functioning. The article is devoted to the platelet activation process. Its lead author is professor of the Department of Medical Physics of MSU, Doctor of Physical and Mathematical Sciences Mikhail Panteleev.
There are two kinds of activated platelets: “ordinary” ones (capable of aggregation) and “super-activated” (procoagulant platelets, able to accelerate coagulation). When activated, the aggregating platelets change their shape from discoid into an amoeboid one, with multiple “legs” (filopodia) to improve interacions and spreading on the surface. These platelets form the main body of the platelet thrombus. The super-activated platelets become spherical and enlarged (they are also called ‘balloons’). They are able to enhance the clot and accelerate the blood clotting reaction. One of the mysteries in the field of hemostasis and thrombosis is how these cells get divided into two kinds when activated? What determines a platelet’s fate? The team of scientists figured out a crucial puzzle of the platelet signaling.
The central player in this decision turned out to be mitochondria. It is believed that mitochondria — the organelles that are present in almost all animal (and plant) cells — including platelets provide them with energy due to redox reactions.
‘But it seems that platelets need mitochondria not only for energy, or even not at all for energy, but for a quick suicide,’ begins Mikhail Panteleev the story.
Scientists managed to show how the platelet’s programmed death (mitochondrial necrosis) follows a chain of processes leading to the transition of the platelets into the super-activated state. In other words, to get super-activated, a platelet must die, as its mission begins from the moment they are ‘dead’. For this reason, platelets are also called “kamikaze cells”.
‘It was not clear before how a platelet makes the decision of what type to become. We have deciphered the sequence of events: how the signal goes within the platelet, and how the cell decides to die,’ Mikhail Panteleyev tells.
Together with the colleagues from Dm. Rogachev Scientific and Medical Center, Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences and the Faculty of Therapeutics, Pirogov Russian National Research Medical University, researchers found that the activation process is as follows. A platelet has many activators, but the chief among them are: collagen, ADP and thrombin. Platelets detect different concentrations of an activator, and respond with a varying frequency of the calcium impulses in the cytoplasm. This phenomenon is called calcium oscillations. Platelets’ mitochondria absorb and store the calcium, and when its concentration exceeds the critical level, the process of the mitochondrial necrosis (a rare version of programmed cell death) of platelets starts: calcium and reactive oxygen species are released from mitochondria, ATPases begin to destroy ATP instead of synthesizing it, the cell cytoskeleton collapses, and the platelet size greatly increases. As a result, at the outer membrane of the enlarged spherical platelet, a lipid called phosphatidylserine appears, which is responsible for rapid blood clotting. And all this is happening within seconds.
Last year, the same group of researchers published in the Molecular BioSystems an article about the theoretical mechanism of mitochondrial necrosis, and in the present paper this process has been experimentally proven.
Moreover, another article by Mikhail Panteleyev and his colleagues from the Faculty of Physics and Faculty of Fundamental Medicine, MSU, was accepted for publication (“Systems biology insights into the meaning of the platelet’s dual-receptor thrombin signaling”). Scientists explain an exciting puzzle of the platelet intracellular signaling structure: it was the first to show that the same activator influences two receptors in the platelet to achieve maximum sensitivity.
