Project Info
Assessing the influence of ADP Release Models on Platelet Aggregation Under Flow
David Montgomery
dmontgomery@mines.edu
Project Goals and Description:
The blood clotting process comprises two main components: platelet aggregation and the biochemical reactions within the coagulation cascade. In the context of extravascular injuries characterized by high shear rates, clot formation begins with the aggregation of shear-activated platelets at the injury site. During the early stages of aggregation, Adenosine diphosphate (ADP) is secreted from platelet dense granules, serving as the primary activator of platelets in the plasma, which causes platelets to change shape, release granule contents, and aggregate. Despite the existence of multiple mathematical models describing ADP release, a comprehensive comparative study evaluating the accuracy of these models has yet to be conducted. This knowledge gap offers an opportunity for further analysis and the potential development of new models. This project aims to leverage our clotFoam software to implement multiscale models of platelet aggregation under various flow conditions. Specifically, we seek to compare the effects of different ADP release models in flows characterized by both low and high shear rates. Our goal is to enhance the efficiency of numerical simulations by gaining insights into how these models perform under varying shear conditions, potentially reducing computation time in our simulations.
More Information:
Grand Challenge: Engineer better medicines.
Wei-Tao Wu, Megan A Jamiolkowski, William R Wagner, Nadine Aubry, Mehrdad Massoudi, and James F Antaki. Multi-constituent simulation of thrombus deposition. Scientific reports, 7(1):1–16, 2017. doi: 10.1038/srep42720.
Karin Leiderman and Aaron L Fogelson. Grow with the flow: a spatial–temporal model of platelet deposition and blood coagulation under flow. Mathematical medicine and biology: a journal of the IMA, 28(1):47–84, 2011. doi: 10.1093/imammb/dqq005.
Reed, G. L., Fitzgerald, M. L., & Polgár, J. (2000). Molecular mechanisms of platelet exocytosis: insights into the “secrete” life of thrombocytes. Blood, The Journal of the American Society of Hematology, 96(10), 3334-3342. doi: 10.1182/blood.V96.10.3334
David Montgomery, Federico Municchi, and Karin Leiderman. clotfoam: An open-source framework to simulate blood clot formation under arterial flow. SoftwareX, 23:101483, 2023. doi: 10.1016/j.softx.2023.101483.
Primary Contacts:
David Montgomery, dmontgomery@mines.edu
Student Preparation
Qualifications
Interested students should have familiarity with scientific computing (MATH 307) and partial differential equations (MATH 455), as well as some previous coding experience in C/C++ or related languages. It's also important for students to be open to learning about the foundational biology related to the problems we're working on.
TIME COMMITMENT (HRS/WK)
3-5
SKILLS/TECHNIQUES GAINED
Students will develop analytical and computational skills through hands-on experience running their own simulations of platelet aggregation using open-source software packages. Given the exploratory nature of the project, students will have the opportunity to refine their research skills and enhance their scientific insight.
MENTORING PLAN
We'll schedule weekly one-hour meetings to help you along the way. In the initial few weeks, we'll delve into understanding the existing models and how they're integrated into the clotFoam software. You'll also get hands-on experience with editing and compiling the software. Once you're comfortable with the software, we'll dive into a mini-project. Your task will be to implement the ADP release model used by Wu et al. Afterward, we'll quantitatively analyze the results using ParaView and Matlab. Following the completion of this mini-project, we'll shift our focus to exploring new ADP release models.
PREFERRED STUDENT STATUS
Sophomore
Junior
Senior