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Dynamics and distribution of immunoglobolin E receptors : a dialog between experiment and theory

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Please use this identifier to cite or link to this item: http://hdl.handle.net/1928/20881

Dynamics and distribution of immunoglobolin E receptors : a dialog between experiment and theory

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Title: Dynamics and distribution of immunoglobolin E receptors : a dialog between experiment and theory
Author: Spendier, Kathrin
Advisor(s): Thomas, James L
Kenkre, Vasudev N
Committee Member(s): Thomas, James L
Kenkre, Vasudev N
Prasad, Sudhakar
Lidke, Diane S
Department: University of New Mexico. Dept. of Physics & Astronomy
Subject(s): mast cells
TIRF
receptor clusters
single-particle tracking
particle coalescence
LC Subject(s): Immunoglobulin E--Receptors.
Mast cells--Immunology.
Cellular signal transduction.
Degree Level: Doctoral
Abstract: This dissertation explores the dynamics and distribution of immunoglobulin E receptors (FceRI) on mast cells by drawing on the techniques of experimental and theoretical physics. The motivation for these investigations is provided by a considerable interest in the transmembrane signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. Experimental investigations quantify the spatiotemporal dynamics of the redistribution of FceRI due to membrane-bound monovalent ligands, using total internal reflection fluorescence microscopy and single-particle tracking. When mast cells contact such substrates, receptor clusters form at cell-substrate contact points. The initial rate of accumulation of receptors into these contact points or cell protrusions is consistent with diffusion-limited trapping. Over longer timescales (>10 s), individual clusters move with both diffusive and directed motion components and eventually coalesce to form a large central receptor patch surrounded by a receptor cluster depletion zone. Detailed analysis of single-particle trajectories show that receptors maintain their diffusivity when confined within receptor clusters, and increase their diffusivity (above that of monomeric unliganded FceRI) in central patches. To study the kinetics of central patch formation, a new coalescence theory described by a melding process, which is not instantaneous, was developed. In these theoretical investigations, the difficult problem of moving boundaries is encountered. To handle the complexity, which stems from boundary growth due to particle melding, the study is divided into three parts. The first is about stationary trapping problems investigated by the standard defect technique, and the second is about a validity study of an adiabatic approximation for moving boundaries. In the last part of this dissertation, a new coalescence theory is developed, which is based on a completely self-consistent approach. Here, the time dependence of the moving boundary is not prescribed but obtained through feedback. Comparison of experiment and theory shows that observed biological cluster coalescence is delayed at early times and occurs at a faster rate at later times than predicted by a simple theory. The incompatibility at early times is addressed by a generalization of the theory to incorporate a time-dependent melding process by a memory concept, which quantitatively explains the observed delay.
Graduation Date: May 2012
URI: http://hdl.handle.net/1928/20881

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