FiberSim

FiberSim performs spatially-explicit simulations of myofilament-level contraction to model sarcomere mechanics by tracking positions and states of myosin heads, actin binding sites, and myosin-binding protein C (MyBP-C).

Key Features:

• Spatially-explicit lattice modeling: Tracks the position and status of each contractile molecule—myosin heads, actin binding sites, and MyBP-C—within a lattice framework.
• MyBP-C regulation: Captures mechanical effects influenced by MyBP-C and models regulation of thick filament transitions by MyBP-C.
• Tension-pCa simulation: Simulates tension-pCa curves with and without regulation of thick filament transitions by MyBP-C.
• Myotrope dose-dependence: Models dose-dependent effects of myotropes including omecamtiv mecarbil and mavacamten.
• Isoform expression effects: Models the impact of different sarcomeric protein isoform expression levels on contractility.
• Custom models and protocols: Supports user-defined models and protocols for varied experimental conditions.
• Computational efficiency: Enables simulations on standard laptop-class hardware without requiring high-performance computing resources.

Scientific Applications:

• Myotrope evaluation: Predicts how myotropes such as omecamtiv mecarbil and mavacamten modulate sarcomere-level contractility.
• Mechanistic sarcomere studies: Explores how modifications in sarcomeric proteins influence muscle contractile mechanics at the myofilament level.
• Isoform and dose-response analysis: Investigates effects of sarcomeric isoform expression and dose-dependence on contractile behavior.
• Tension-pCa analysis: Generates tension-pCa curves to compare conditions with and without MyBP-C–mediated thick filament regulation.

Methodology:

Uses a spatially-explicit lattice framework that tracks positions and states of myosin heads, actin binding sites, and MyBP-C; simulates tension-pCa curves; models MyBP-C regulation of thick filament transitions; and implements dose-dependence of myotropes and effects of isoform expression, with support for user-defined models and protocols.