A phenomenological particle‐based platelet model for simulating filopodia formation during early activation

Abstract

We developed a phenomenological three-dimensional (3D) platelet model to characterize the filopodia formation observed during early stage platelet activation. Departing from continuum mechanics based approaches; this coarse-grained molecular dynamics (CGMD) particle-based model can deform to emulate the complex shape change and filopodia formation that platelets undergo during activation. The platelet peripheral zone is modeled with a two-layer homogeneous elastic structure represented by spring-connected particles. The structural zone is represented by a cytoskeletal assembly comprising of a filamentous core and filament bundles supporting the platelet’s discoid shape, also modeled by spring-connected particles. The interior organelle zone is modeled by homogeneous cytoplasm particles that facilitate the platelet deformation. Non-bonded interactions among the discrete particles of the membrane, cytoskeletal assembly, and the cytoplasm are described using the Lennard-Jones potential with empirical constants. By exploring the parameter space of this CGMD model, we have successfully simulated the dynamics of varied filopodia formations. Comparative analyses of length and thickness of filopodia show that our numerical simulations are in agreement with experimental measurements of flow-induced activated platelets.

A multiscale biomechanical model of platelets: Correlating with in-vitro results

“…A mechanotransduction process of hemodynamic forces had to be established from the membrane to the complex intracellular constituents, particularly the cytoskeleton that may prompt spontaneous filopodia formation and growth upon flow-induced activation. Extending our previous efforts, the present work fills this gap (Soares, Gao et al 2013; Pothapragada, Zhang et al 2015).…”

“…At extreme conditions such as high shear stresses in cardiovascular devices and in pathological flows fields, highly-resolved experiments were hardly performed. Our group is actively conducting such flow experiments where platelet properties are studied under the relevant flow conditions (Zhang, Zhang et al 2014; Pothapragada, Zhang et al 2015), as well as developing non-invasive methods to test the mechanical properties of platelets (Leung, Lu et al 2015). Additionally, platelet sensitivity to flow stresses and subsequent flow-induced activation greatly increases the difficulty for directly measuring platelets under extreme flow patterns.…”

Platelet “first responders” in wound response, cancer, and metastasis

“…These platelet recognition properties include the exposure of the subendothelial basement membrane or underlying matrix induced by wounding or endothelial retraction [18–23]. The rapid formation of filopodia facilitated by a variety of adhesion receptors linked to a highly reactive cytoskeleton helps maximize dynamic surface contacts and the rapid response rate of platelets [24–31]. …”

Scalability Test of multiscale fluid–platelet model for three top supercomputers

“…By extending our previous efforts for modeling platelets under viscous shear flow conditions at multiple spatio-temporal scales [6-9], we develop a multiscale benchmark model for assessing the performances of three supercomputers for understanding multiscale phenomena of complex biological systems. In this model, we cover two spatio-temporal scales: (i) the microscale flow regime using dissipative particle dynamics (DPD) to describe the bulk transfer of viscous blood flow [10]; and, (ii) the nanoscale platelet model using coarse-grained molecular dynamics (CGMD) to describe the cellular scale structural details of a platelet such as membranous morphology, cytoplasmic biorheology, cytoskeletal filaments and the flow-mediated cellular mechanotransduction of hemodynamic stresses across the platelet surface and through the cytoskeleton [6].…”

“…We propose a multiscale numerical approach for modeling the multiscale fluid-platelet phenomena. The proposed approach utilizes a multiscale model where dissipative particle dynamics is coupled with molecular dynamics to describe flow induced mechanotransduction processes and biochemical events spanning the vast range of spatial and temporal scales characterizing blood flow-induced clotting and thrombosis [6-9]. …”