Semester
Spring
Date of Graduation
2023
Document Type
Dissertation
Degree Type
PhD
College
Eberly College of Arts and Sciences
Department
Mathematics
Committee Chair
Adam Halasz
Committee Member
Marjorie Darrah
Committee Member
Jessica Deshler
Committee Member
Harvey Diamond
Committee Member
Casian Pantea
Committee Member
Tudor Stanescu
Abstract
I use mathematical modeling to understand aspects of molecular processes in living cells. Specifically, we look at the first few steps in cell signaling. Signal initiation requires that receptors located on the cell membrane bind together to form dimers. Microscopic imaging of receptors on the cell membrane revealed that receptors tend to accumulate in small areas (clusters). Studies also show that the membrane has a complex landscape consisting of domains and barriers of various origin.
Here we study the way receptor dimerization is influenced by domains on the cell membrane. Our underlying hypothesis is that the physical and chemical properties of certain types of microdomains cause the accumulation of receptors. We know that dimerization increases the tendency of receptors to accumulate in attractive domains. However, it is not clear whether this is enough to explain the dramatic increase in cluster sizes observed during signaling. We aim to understand whether receptors accumulate more or less uniformly in all domains (of the appropriate type) or there are effects that favor non-uniform accumulation, resulting in fewer, larger clusters upon increased and / or non-uniform ligand concentrations.
We study compartment-based models representing multiple domains on the cell membrane, each with a network of chemical reactions derived from VEGF signal initiation. Our central result is a complete analytical solution of the two-compartment model. We establish that the closed version of this system has a unique steady state. Further analysis led us to a four-domain structure, with two low density domains in contact with each other, each surrounding a small, high affinity domain. This system has the potential to concentrate liganded receptors in one of the high affinity domains in response to a mild difference in VEGF concentrations.
Recommended Citation
Al-Maliki, Basim Mohammed, "Stability properties of a system of receptors in the presence of attractive domains" (2023). Graduate Theses, Dissertations, and Problem Reports. 11677.
https://researchrepository.wvu.edu/etd/11677
Embargo Reason
Publication Pending