Single-Cell Biophysics: Measurement, Modulation, and Modeling

Single-Cell Biophysics: Measurement, Modulation, and Modeling

Poster Abstracts

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.

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