Mechanical Property and Phenotype Characterization of an in vitro Model for Afterload-triggered Cardiac Hypertrophy

<p>Hypertrophic Cardiomyopathy (HCM) is an inherited cardiomyopathy disease that affects approximately 1 in 500 to 1 in 200 people. Although abundant evidence has shown that HCM is related to sarcomere genetic mutations, recent research has also revealed that conditions that increase cardiac afterload, like obesity and hypertension, worsen HCM patients’ prognosis. Among research models of HCM, in vitro models that use patient-derived induced pluripotent stem cell (iPSC) differentiated cardiomyocytes are especially promising because the unlimited supply of iPSC can allow many studies to be performed under reproducible conditions. In prior studies of afterload-related phenotypes in HCM and other iPSC-based heart disease models, soft substrates like Polydimethylsiloxane (PDMS) or hydrogels have been used as stiffness matrix. However, these substrates that have constant mechanical properties have the disadvantage of being unable to mimic dynamic changes in cells’ environment that happen in the body as a result of hypertension Thus, magnetorheological elastomers (MREs), which change their stiffness in response to magnetic fields, have been developed as a next-generation substrate for cardiac mechanobiology studies. In this thesis, I characterized how the mechanical properties of MRE vary with respect to substrate geometry, and I am currently in the process of applying these substrates to study how cardiomyocytes and cardiac fibroblasts respond to dynamic stiffness changes. To characterize the mechanical properties and get the highest stiffness range of MRE substrates that we use in our <em>in vitro</em> model, Indentation testing and shear testing were performed on MREs with different dimensions and densities of magnetic-responsive iron particles. For the characterization of the shear modulus, I developed a custom method to replace rheology. I also verified the cytocompatibility of MREs. I am currently using MREs with iPSC-cardiomyocytes and primary cardiac fibroblasts to study how dynamic mechanical loading affects cellular hypertrophy. As a result, Higher magnetic particle doping weight percentage and higher magnetic fields increased MRE stiffness. In contrast, MRE thickness did not affect the shear modulus upon magnetization. Finally, the MREs were proven non-toxic to cells, and representative images of the immunostaining of the cardiomyocytes were acquired. Based on this, we are aiming at doing some preliminary studies on pathological phenotypes of heart disease (e.g. cell hypertrophy) with cardiomyocytes under increased afterload.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Mechanical Engineering & Materials Science

Year dc:date.available

2024

Author dc:creator

• Sun, Yuwen

Contributors dc:contributor

• Dr. Nathaniel Huebsch
• Dr. Guy Genin, Dr. Amit Pathak

• Magnetorheological Elastomers
• Cardiac Hypertrophy
• Polydimethylsiloxane
• in vitro model
• Biomedical Engineering and Bioengineering
• Materials Science and Engineering

Statement dc:rights

• I have not registered my thesis with the U.S. Copyright Office, but intend to later.

Language dc:language

English (en)

Identifier

https://openscholarship.wustl.edu/eng_etds/1006

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:eng_etds-2073