The Cardiac Cell Under the Mathematical Microscope — ASN Events
  1. Schedule
  2. Session 2: Modelling and Visualisation
  3. The Cardiac Cell Under the Mathematical Microscope

The Cardiac Cell Under the Mathematical Microscope (#9)

Vijay Rajagopal 1 2 , Gregory Bass 2 , Shouryadipta Ghosh 1 2 , Eric Hanssen 3 , Edmund J Crampin 2 4 5
  1. Cell Structure and Mechanobiology Group, Department of Mechanical Engineering, University of Melbourne, Parkville, VIC, Australia
  2. Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Parkville, VIC, 3010
  3. Advanced Microscopy Facility, Bio21 Molecular Science and Biotechnology Institute,, University of Melbourne, Parkville, VIC, 3010
  4. School of Medicine, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, 3010
  5. School of Mathematics and Statistics, Faculty of Science, University of Melbourne, Parkville, VIC, 3010

The cells that make up our hearts have a highly specialised organisation. These structures 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 Ca2+ during the rising phase of the transient (first 30 ms after initiation).

 We demonstrate in this study that: (i) heterogeneities in the Ca2+ 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 Ca2+ can appear in line scan data. Using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the Ca2+ 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.