Mechanical Modeling of Cardiac Fibrosis With Explicit Spatial Representation of Cellular Structure and Collagen...

Area of Science:

• Cardiovascular Research
• Biomedical Engineering
• Computational Biology

Background:

• Cardiac fibrosis is a pathological remodeling process impairing cardiac function.
• It involves collagenous tissue replacing myocytes (replacement fibrosis) or expanding between them (interstitial fibrosis).
• Associated remodeling includes myocardial stiffening and collagen alignment, with mechanical impacts under investigation.

Purpose of the Study:

• To investigate the microscale mechanical effects of fibrotic remodeling using a computational model.
• To assess the individual and combined impacts of structural changes, stiffness, and collagen alignment during contraction and stretch.

Main Methods:

• Developed a computational model with explicit myocyte and collagen geometries.
• Simulated replacement fibrosis by substituting myocytes with extracellular matrix.
• Modeled interstitial fibrosis by increasing transverse cell spacing, combined with altered stiffness and collagen alignment.

Main Results:

• Structural changes alone significantly increased myocyte stress during contraction (e.g., 53.9 kPa for interstitial space vs. 30.9 kPa baseline).
• Collagen alignment and myocyte stiffening mitigated these increased stress levels.
• Myocyte stiffening, rather than matrix stiffening, was the primary contributor to overall tissue stiffening.

Conclusions:

• Fibrotic remodeling elevates stress in surviving myocytes, potentially impairing function.
• Myocyte stiffening and collagen alignment may act as compensatory mechanisms, despite increasing tissue stiffness.
• Microscale modeling integrated with experimental data is crucial for understanding fibrotic remodeling's mechanical consequences.