Interactions of Cardiomyocytes and Myofibroblasts: An Experimental and Theoretical Model Study

Cardiomyocytes and fibroblasts make up the majority of cells in natural myocardium. While cardiomyocytes are primarily responsible for the mechanical contraction, fibroblasts are responsible for maintaining the extracellular matrix and tissue compliance. In response to pathologies such as hypertension or infarction, fibroblasts in the heart can convert to myofibroblasts, a larger and more contractile phenotype between a fibroblast and a smooth muscle cell. Myofibroblasts are essential to wound healing, but can change the compliance and functioning of heart tissue and can produce pathological fibrosis, formation of excess fibrous connective tissue. In developing therapeutic approaches it is essential to understand how myofibroblasts modulate the electromechanical functions of fibrotic heart. In this dissertation, the problem is studied by developing computational and experimental models of heart muscle with randomly distributed varying ratios of myofibroblasts. The experimental model consists of engineered heart tissues assembled from embryonic cardiomyocytes and containing defined fractions of myofibroblasts randomly distributed throughout the tissue. The computational model is formulated at the cellular level taking into account individual cardiomyocytes and myofibroblasts to yield the pattern of impulse spread as modulated by the presence of myofibroblasts acting either as insulators or resistors. The excitatory impulse activates the contraction of individual viscoelastic cells that are mechanically linked to other cells and the extracellular matrix. The results give insight into the mechanical and electrical modulation of engineering heart tissue by myofibroblasts.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Mechanical Engineering and Materials Science

Year dc:date.available

2012

Author dc:creator

• Abney, Teresa

Contributors dc:contributor

• Guy Genin

• Mechanical engineering
• Biomechanics
• Biomedical engineering
• cardiac electromechanics
• cardiac electrophysiology
• cardiac mechanics
• fibrosis
• myofibroblasts

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K7FB511G

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1676