RT Journal Article
SR Electronic
T1 Analysis of microvascular thrombus mechanobiology with a novel particle-based model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.07.447380
DO 10.1101/2021.06.07.447380
A1 Anastasia A. Masalceva
A1 Valeriia N. Kaneva
A1 Mikhail A. Panteleev
A1 Fazoil Ataullahanov
A1 Vitaly Volpert
A1 Ilya Afanasyev
A1 Dmitry Yu. Nechipurenko
YR 2021
UL http://biorxiv.org/content/early/2021/06/07/2021.06.07.447380.abstract
AB Platelet accumulation at the site of vascular injury is regulated by soluble platelet agonists, which induce various types of platelet responses, including integrin activation and granule secretion. The interplay between local biochemical cues, mechanical interactions between platelets and macroscopic thrombus dynamics is poorly understood.Here we describe a novel computational model of microvascular thrombus formation for detailed analysis of thrombus mechanics. Adopting a previously developed two-dimensional particle-based model focused on the thrombus shell formation, we revise it to introduce platelet agonists. Blood flow is simulated via computational fluid dynamics approach. In order to model soluble platelet activators, we apply Langevin dynamics to a large number of non-dimensional virtual particles. Taking advantage of the available data on platelet dense granule secretion kinetics, we model platelet degranulation as a stochastic agonist-dependent process.The new model qualitatively reproduces enhanced thrombus formation due to granule secretion in line with in vivo findings and provides a mechanism for thrombin confinement at the early stages of aggregate formation. Our calculations also predict that release of dense granules results in additional mechanical stabilization of the inner layers of the thrombus. Distribution of the inter-platelet forces throughout the aggregate reveals multiple weak spots in the outer regions of thrombus, which are expected to result in mechanical disruptions at the later stages of thrombus formation.Competing Interest StatementThe authors have declared no competing interest.