139 / 155
Single-Cell Biophysics: Measurement, Modulation, and Modeling
Poster Abstracts
134
72-POS
Board 36
The Cardiac Cell under the Mathematical Microscope
Vijay Rajagopal
1
, Gregory Bass
4
, Shouryadipta Ghosh
1
, Eric Hanssen
5
, Edmund Crampin
2,3,4
.
1
University of Melbourne, Melbourne, VIC, Australia,
2
University of Melbourne, Parkville,
Australia,
5
University of Melbourne, Melbourne, VIC, Australia.
3
University of Melbourne,
Melbourne, Australia,
4
University of Melbourne, Melbourne, Australia,
The cells that make up our hearts have a highly specialised organisation. This organisation can
undergo drastic changes in patients with heart disease, but a fundamental understanding of the
significance of these changes and how they develop is lacking. We are developing methods to
integrate state-of-the-art structural microscopy data and biophysical modeling techniques in
order to gain new insights into the role of spatial organization in cardiac cell systems biology.
Here we present a new method to computationally integrate electron microscopy and
immunofluorescence data of heart cell ultrastructure to build a detailed model of the heart cell.
We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR
clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria that were
collected from rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated
reaction-diffusion of Ca
2+
during the rising phase of the transient (first 30 ms after initiation).
We demonstrate in this study that: (i) heterogeneities in the Ca
2+
transient are not only due to
heterogeneous distribution and clustering of mitochondria; (ii) but also due to heterogeneous
distribution of RyR clusters; Further, we show that: (iii) these structure-induced heterogeneities
in Ca
2+
can appear in line scan data. Using our unique method for generating RyR cluster
distributions, we demonstrate the robustness in the Ca
2+
transient to differences in RyR cluster
distributions measured between rat and human cardiomyocytes.
We also discuss our on-going development of a complete 3D model of a heart cell and our
investigations into the impact of cardiac ultrastructural remodeling on function in diabetic
cardiomyopathy.