Cilia are cellular organelles that generate microfluidic flow at multiple sites in the body. They are important for health due to their critical roles in mucus clearance in the respiratory tract, circulation of cerebrospinal fluid in the ventricles of the brain, transport of ova in the Fallopian tubes, and left-right patterning of the body. Nonetheless, standards for basic mechanical phenotyping of cilia are still relatively undefined. The aim of this thesis is to develop an experimental and conceptual framework for comprehensive ciliary phenotyping. Towards that aim, we pursue three major lines of investigation involving ciliary physiology, pathophysiology, and measurement.
Our investigation into pathophysiology looks at the possibility of quantifying intermediate ciliary flow defects. Specifically, we investigate subtle changes to ciliary flow generated by genetic knockdown of ciliary proteins, alterations in chemical signaling, and changes to the viscous environment of ciliated surfaces. We additionally quantify the onset of ciliary flow in the context of normal development.
Secondly, we demonstrate the use of optical coherence tomography (OCT)-based velocimetry techniques for the measurement of cilia-driven fluid flow. In particular, we focus on a class of correlation-based techniques that utilizes the complex OCT signal to recover the total speed of fluid flow. We analyze and extend these techniques towards directional velocity measurements, and eventually towards quantification of the full three-dimensional, three vector component velocity flow field.
Finally, our investigation into ciliary physiology involves the development of a simplified model of ciliary function. Building on previous models of ciliated surfaces as shearing elements, we develop our "treamdill-in-a-pool" model of ciliated surface that also incorporates the dynamics of functional reserve and failure. These efforts motivate the measurement of three important physical parameters, flow rate, force, and mechanical power output, under conditions of increased viscous loading.
Building on these themes, we propose a comprehensive, optical-imaging based approach towards quantifying flow, force, and power in the context of ciliary performance and failure. We present a method of quantifying these mechanical properties not by direct measurement, but rather by inference from the fluid flow field that is generated by ciliary action. In all, we propose a new theoretical and experimental framework for biomechanical phenotyping of ciliated surfaces.
|Advisor:||Choma, Michael A.|
|School Location:||United States -- Connecticut|
|Source:||DAI-B 77/07(E), Dissertation Abstracts International|
|Keywords:||Cilia, Microfluidics, Mucociliary Clearance, Optical Coherence Tomography, Pulmonary Physiology, Velocimetry|
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