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A method to replicate the microstructure of heart tissue in vitro using DTMRI-based cell micropatterning
Nima Badie1, Lisa Satterwhite, Nenad Bursac
1Department of Biomedical Engineering, Duke University, 3000 Science Drive, 136 Hudson Hall, Durham, NC, 27708, USA.
Annals of Biomedical Engineering
|October 7, 2009
Summary
This study introduces a new method combining diffusion tensor magnetic resonance imaging (DTMRI) and cell micropatterning to create realistic tissue structures. This technique accurately replicates cardiac fiber directions in cell cultures for studying heart function.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Cardiovascular Research
Background:
- Realistic tissue microstructure is crucial for understanding cardiac function.
- Current cell culture methods often fail to replicate complex in vivo tissue architecture.
- Diffusion tensor magnetic resonance imaging (DTMRI) provides detailed information on tissue microstructure.
Purpose of the Study:
- To develop a novel cell culture methodology integrating DTMRI and cell micropatterning.
- To fabricate cell monolayers that accurately mimic native tissue cross-sectional structure.
- To enable systematic studies of intramural structure-function relationships in cardiac tissue.
Main Methods:
- DTMRI-measured cardiac fiber directions were used to create soft-lithography photomasks.
- Silicone stamps generated fibronectin patterns to guide cellular alignment.
- Neonatal rat ventricular myocytes (NRVMs) were cultured on patterned substrates.
Main Results:
- Confluent, electrically coupled NRVM monolayers were established within 6 days.
- Cell alignment in subregions accurately replicated DTMRI-measured fiber directions (7.2 +/- 4.1 degrees error).
- Adjusting fibronectin patterns altered cell elongation, gap junction distribution, and cellular disarray.
Conclusions:
- The novel methodology successfully replicates cardiac tissue microstructure in vitro.
- This technique allows for controlled manipulation of cellular organization and its effect on electrical propagation.
- It provides a powerful platform for investigating structure-function relationships in healthy and diseased hearts.
