Date of Award

Summer 8-27-2021

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Soman, Pranav

Keywords

Calcium signaling, Computational modeling, Mechanical stimulation, Network connectivity, Osteocyte, Signal propagation

Subject Categories

Biomedical Engineering and Bioengineering | Engineering

Abstract

Bone is a highly complex and organized tissue that is composed of an abundance of cells including the osteocyte. While it is known that osteocytes are responsible for the control of the bone remodeling process and the maintenance of calcium (Ca2+) homeostasis using their network of gap junction connections, their complete role is not yet fully understood. It is also known that various bone related diseases as well as cancer demonstrate an alteration of Ca2+ homeostasis during the progression of the disease. Previous researchers have combined computational modeling with experimental studies to gain a better understanding of cell-to-cell Ca2+ signaling within the osteocyte network in hopes of developing new diagnostic and therapeutic methods for bone related diseases. In this work, we connect and expand previously developed computational models of Ca2+ propagation within cell populations with the goal to gain more insight of cell-to-cell signaling amongst in vitro osteocyte network cultures that mimic their native environment. Our work demonstrates that unique signal response patterns displayed amongst osteocyte networks are attributed to varying specific kinetic parameters. We were also able to determine the arrangement of two connected osteocytes with differing signal response patterns from our experimental studies using our computational model. The insight of osteocyte heterogeneity gained can contribute to future efforts to develop diagnostic and therapeutic treatments for bone related diseases and cancer.

Access

Open Access

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