Microheterogeneity-induced conduction slowing and wavefront collisions govern macroscopic conduction behavior: A...

Area of Science:

• Cardiovascular physiology
• Biophysics
• Computational biology

Background:

• Cardiac arrhythmias are linked to tissue heterogeneities like fibrosis.
• The precise impact of microscopic structural variations on tissue conduction is not well understood.

Purpose of the Study:

• To investigate how acellular microheterogeneities influence macroscopic conduction in excitable tissues.
• To explore mechanisms of conduction under normal and reduced excitability using combined in vitro and in silico methods.

Main Methods:

• Engineered-excitable Ex293 cell monolayers with patterned nonconductive micro-obstacles were used.
• Paired in vitro and in silico studies examined conduction mechanisms.
• Obstacle size to strand width ratio was varied to assess effects on conduction.

Main Results:

• Increased micro-obstacle size led to significant conduction slowing (up to 23.6%) and increased wavefront curvature anisotropy.
• Microscale behaviors like local conduction slowing and wavefront merging, rather than bulk conductivity or tortuosity, explained macroscopic changes.
• Reduced excitability exacerbated conduction slowing and reversed wavefront curvature anisotropy due to non-uniform microscale effects.

Conclusions:

• Microscopic structural heterogeneities critically impact macroscopic conduction in excitable tissues.
• Understanding these microscale mechanisms provides insights into cardiac arrhythmias in conditions like fibrotic heart disease.
• The developed experimental and computational platform offers valuable mechanistic insights.