I am working
to help bridge the gap between the structure and function of 2D
cardiomyocyte monolayers and that of an actual 3D heart. Using data
obtained by from an intact heart with diffusion tensor magnetic
resonance imaging (DTMRI), general fiber directions and patterns
can be extracted for any cross-section. Using these same patterns
to guide the growth and positioning of cultured cardiomyocytes,
we hope to culture a 2D monolayer that resembles the projected cross-section
of the native tissue in both structure and function. Ultimately,
we wish to use optical mapping to provide insight into the complex
dynamics of impulse propagation and structure-dependent arrhythmogenicity.
Fig. 1.
Micropattern Development
(A) DTMRI-measured in-plane fiber directions of three murine ventricular
cross-sections, shown using circular colormap from B. (B) Angle
map of a transverse ventricular cross-section in MATLAB. For each
pixel, the white line and pixel color denote fiber direction and
angle relative to x-axis, respectively.
Fig. 2.
Formation of realistic cardiac microstructure in anisotropic slice
cultures.
(A-C) Plated cells were found to attach and align along the underlying
fibronectin lines and spread to form confluent cardiac fibers by
day 6. (D) Composite image of entire micropatterned slice culture.
(E) Close-up of four adjacent pixels delineated by dashed line and
underlying fibronectin pattern (green, inset). Note abrupt changes
in cardiac fiber directions in neighboring pixels without loss of
cell confluence. Red, sarcomeric a-actinin; green, connexin43; blue,
nuclei.
Movie 1.
Isopotential movie illustrating ramped rapid pacing-induced conduction
block.
Conduction block occurs at the anterior edge of the junction between
the septum and right ventricular free wall junction. Pacing was
applied in the center of the right ventricular free wall (pacing
times denoted by white flashes). Red indicates action potential
peak, blue indicates rest.
