| dc.identifier.uri | http://hdl.handle.net/11401/76967 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Thrombosis in cardiovascular diseases and prosthetic cardiovascular devices can be potentiated by pathological flow patterns that enhance hemostatic responses including platelet activation, aggregation, and adhesion. Platelets upon activation react to pathological shear stresses with complex biochemical and morphological changes, aggregate, and adhere to blood vessels or device surfaces to form thrombi. Computational modeling and simulation are extensively employed to study the shear-induced platelet activation. Numerical simulations of this complex process based on Computational Fluid Dynamics (CFD) treat blood as a continuum and solve the Navier-Stokes equations to resolve the process to μm scales level. Due to the limited scales range, CFD is not able to address the subsequent biomechanical interactions of blood’s individual constituents, and molecular mechanisms governing platelet activation which occur at the nm scales. To bridge the gap from the 10 nm to the 100 μm between cellular/molecular scales and macroscopic flow scales, this dissertation presents a novel multiscale modeling approach based on discrete particle methods that permits the investigation of such complex phenomena by coupling the macroscopic flow conditions with the cellular and molecular effects of platelet activation. The multiscale approach incorporates (i) top scale blood plasma model with DPD method, with length scales down to μm, where multiple platelets – each composed of an ensemble of particles – are suspended in a discrete particle medium with viscous fluid properties; and (ii) bottom scale platelet model employing CGMD method down to nm scale, in which platelet with multiple sub-components (actin filaments cytoskeleton, bilayer membrane, and cytoplasm) evolves during activation characterized by pseudopodia formation and shape change. The fully interactive micro-nano multiscale model transmits the mechanical stress across the scales: individual platelet is activated in response to fluid shear stress at the bottom scale, where the actin filaments exposed to the highest mechanical stresses elongate and induce pseudopodia formation; the blood plasma dynamics at the top scale is then affected by the activated platelet with morphological changes. Aided with state-of-the-art HPC techniques, this multiscale shear-induced platelet activation model offers a significant contribution to elucidate the underlying mechanisms of thrombus formation agonized by mechanical stimuli. | |
| dcterms.abstract | Thrombosis in cardiovascular diseases and prosthetic cardiovascular devices can be potentiated by pathological flow patterns that enhance hemostatic responses including platelet activation, aggregation, and adhesion. Platelets upon activation react to pathological shear stresses with complex biochemical and morphological changes, aggregate, and adhere to blood vessels or device surfaces to form thrombi. Computational modeling and simulation are extensively employed to study the shear-induced platelet activation. Numerical simulations of this complex process based on Computational Fluid Dynamics (CFD) treat blood as a continuum and solve the Navier-Stokes equations to resolve the process to μm scales level. Due to the limited scales range, CFD is not able to address the subsequent biomechanical interactions of blood’s individual constituents, and molecular mechanisms governing platelet activation which occur at the nm scales. To bridge the gap from the 10 nm to the 100 μm between cellular/molecular scales and macroscopic flow scales, this dissertation presents a novel multiscale modeling approach based on discrete particle methods that permits the investigation of such complex phenomena by coupling the macroscopic flow conditions with the cellular and molecular effects of platelet activation. The multiscale approach incorporates (i) top scale blood plasma model with DPD method, with length scales down to μm, where multiple platelets – each composed of an ensemble of particles – are suspended in a discrete particle medium with viscous fluid properties; and (ii) bottom scale platelet model employing CGMD method down to nm scale, in which platelet with multiple sub-components (actin filaments cytoskeleton, bilayer membrane, and cytoplasm) evolves during activation characterized by pseudopodia formation and shape change. The fully interactive micro-nano multiscale model transmits the mechanical stress across the scales: individual platelet is activated in response to fluid shear stress at the bottom scale, where the actin filaments exposed to the highest mechanical stresses elongate and induce pseudopodia formation; the blood plasma dynamics at the top scale is then affected by the activated platelet with morphological changes. Aided with state-of-the-art HPC techniques, this multiscale shear-induced platelet activation model offers a significant contribution to elucidate the underlying mechanisms of thrombus formation agonized by mechanical stimuli. | |
| dcterms.available | 2017-09-20T16:51:33Z | |
| dcterms.contributor | Yin, Wei | en_US |
| dcterms.contributor | Bluestein, Danny | en_US |
| dcterms.contributor | Balazsi, Gabor | en_US |
| dcterms.contributor | Harrison, Robert. | en_US |
| dcterms.creator | Gao, Chao | |
| dcterms.dateAccepted | 2017-09-20T16:51:33Z | |
| dcterms.dateSubmitted | 2017-09-20T16:51:33Z | |
| dcterms.description | Department of Biomedical Engineering | en_US |
| dcterms.extent | 146 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76967 | |
| dcterms.issued | 2016-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:51:33Z (GMT). No. of bitstreams: 1
Gao_grad.sunysb_0771E_13059.pdf: 6546753 bytes, checksum: 5b2159cd7d19968d3b1e638bf50cd15e (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Biomedical engineering | |
| dcterms.title | Multiscale Particle-Based Modeling of Mechanotransduction Process in Flow-Induced Platelet Activation using Dissipative Particle Dynamics and Coarse Grained Molecular Dynamics | |
| dcterms.type | Dissertation | |
