Publication Date

2014-05-07

Availability

Open access

Embargo Period

2016-05-07

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical Engineering (Engineering)

Date of Defense

2014-04-04

First Committee Member

Chun-Yuh Charles Huang

Second Committee Member

Francesco Travascio

Third Committee Member

Alicia Renee Jackson

Abstract

Extracellular adenosine triphosphate (ATP) released from cells can mediate a diverse number of biological responses, such as cell secretion, inflammation, and immune reactions through signaling pathways. According to Wang et al. (2013), the extracellular ATP concentration has been measured to accumulate to a high level in the nucleus pulposus (NP) region in the intervertebral disc (IVD), approximately 165 ?M. Since extracellular ATP is involved in a variety of cellular activities, the role of ATP distribution and accumulation in the IVD should be investigated. The objective of this study is to examine the effects of mechanical compression on the distribution of extracellular ATP and its adenine derivatives in the IVD using triphasic mechano-electrochemical theory. This theory describes the mechanical behavior and transport phenomena of charged hydrated soft tissue such as the IVD. Michaelis-Menten kinetics was used to model ATP hydrolysis and incorporated into a finite element model. Experiments were performed to measure Michaelis-Menten parameters of annulus fibrosus (AF) and NP cells. Results of the ATP hydrolysis experiments show that the maximum reaction velocity, Vmax, for AF cells is significantly greater than the value for NP cells. Thus, the extracellular ATP hydrolysis rate for AF cells could be significantly greater than the rate for NP cells. By comparing the results with the findings reported by Wang et al. (2013), the theoretical analysis indicated that mechanical loading may promote ATP hydrolysis and induce an intrinsic cellular response. Based on a finite element model, this study simulates the distribution of extracellular ATP and its adenine derivatives in the IVD under mechanical loading.

Keywords

IVD; ATP; compression; Michaelis-Menten; numerical simulation

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