Christopher Chen

Optimizing a 2D Culture Device for Characterization of iPSC-derived Cardiomyocytes

PROJECT DESCRIPTION
Cardiomyocyte (CM) culture is a useful platform to model cardiac biology and disease. However, iPSC-derived CMs in 2D often have heterogeneous characteristics both within and between differentiations.  This is, in part, due to the relatively immature state of these cells. Most notably, these cells lack uniform and aligned sarcomere structures. Using microfabrication techniques, this project aims to optimize a 2D CM culture device that promotes sarcomere alignment and uniformity. This will enable the functional characterization of CMs derived from isogenic iPSC cell lines harboring various sarcomere mutations in order to better understand how these mutations cause disease. These devices could also serve as a platform to test therapies for said mutations. Specifically, this project will develop a protein-micropattern fabrication protocol for use in CM culture. Additionally, the substrate stiffness of this culture platform can be experimentally modified to optimize substrate elasticity for sarcomere development. Sarcomere assessment will then be employed in various culture conditions via microscopy and computational analysis.

LABORATORY MENTOR
Mike McLellan and Xining Gao

RESEARCH GOALS
– Fabricate culture substrates with a variety of protein micropatterns via microcontact printing
– Experimentally control PDMS culture substrate stiffness, quantify substrate stiffness
– Study the impact of micropattern geometry/substrate stiffness on sarcomere development – optimize conditions for sarcomere development
– Characterize morphological and functional differences between wildtype and mutant CMs

LEARNING GOALS
– The researcher will develop technical skills related to cardiac tissue engineering as well as more general scientific skills such as iterative design and hypothesis development.
– This student will learn stem cell maintenance and differentiation, microfabrication techniques, PDMS device fabrication, microscopy, immunofluorescence, and functional cardiomyocyte assessment via computational analysis techniques.

Learn more about Professor Chen on his faculty page.