{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T02:45:23Z","timestamp":1770777923684,"version":"3.50.0"},"reference-count":71,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T00:00:00Z","timestamp":1715472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2022-1115"],"award-info":[{"award-number":["075-15-2022-1115"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>In injured arteries, platelets adhere to the subendothelium and initiate the coagulation process. They recruit other platelets and form a plug that stops blood leakage. The formation of the platelet plug depends on platelet activation, a process that is regulated by intracellular calcium signaling. Using an improved version of a previous multiscale model, we study the effects of changes in calcium signaling on thrombus growth. This model utilizes the immersed boundary method to capture the interplay between platelets and the flow. Each platelet can attach to other platelets, become activated, express proteins on its surface, detach, and\/or become non-adhesive. Platelet activation is captured through a specific calcium signaling model that is solved at the intracellular level, which considers calcium activation by agonists and contacts. Simulations reveal a contact-dependent activation threshold necessary for the formation of the thrombus core. Next, we evaluate the effect of knocking out the P2Y and PAR receptor families. Further, we show that blocking P2Y receptors reduces platelet numbers in the shell while slightly increasing the core size. An analysis of the contribution of P2Y and PAR activation to intraplatelet calcium signaling reveals that each of the ADP and thrombin agonists promotes the activation of platelets in different regions of the thrombus. Finally, the model predicts that the heterogeneity in platelet size reduces the overall number of platelets recruited by the thrombus. The presented framework can be readily used to study the effect of antiplatelet therapy under different physiological and pathological blood flow, platelet count, and activation conditions.<\/jats:p>","DOI":"10.3390\/computation12050099","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T06:59:32Z","timestamp":1715756372000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intraplatelet Calcium Signaling Regulates Thrombus Growth under Flow: Insights from a Multiscale Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Anass","family":"Bouchnita","sequence":"first","affiliation":[{"name":"Department of Mathematical Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA"}]},{"given":"Vitaly","family":"Volpert","sequence":"additional","affiliation":[{"name":"Institut Camille Jordan, UMR 5208 CNRS, University Lyon 1, 69622 Villeurbanne, France"},{"name":"S.M. Nikolsky Mathematical Institute, Peoples Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow 117198, Russia"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1538-7836.2009.03401.x","article-title":"Dynamics of platelet thrombus formation","volume":"7","author":"Jackson","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/jth.13280","article-title":"Transport physics and biorheology in the setting of hemostasis and thrombosis","volume":"14","author":"Brass","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1172\/JCI26987","article-title":"Thrombus formation in vivo","volume":"115","author":"Furie","year":"2005","journal-title":"J. Clin. 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