Force-Feedback and Load Sharing Mechanisms in Cardiac Myosin II Ensembles Revealed by Motor-Specific Perturbations

Authors

• Omayma Alazzam, University of Mississippi
• Md. Amzadul Hoque Chowdhury, University of Mississippi
• Heath M. Stevens, University of Mississippi

Document Type

Data Set

Publication Date

6-17-2026

Abstract

Myosin II motors within ensembles exhibit emergent force-generating behavior that varies based on ensemble size and makeup. However, the mechanisms by which myosins within ensembles sense and modulate behavior due to local and systemic changes in motor behavior, and concomitantly mechanics, remains unclear. To understand how myosin kinetics alter ensemble-level force generation, we employ myosin inotropes, specifically Mavacamten (MAVA) and Omecamtiv Mecarbil (OM), to pointedly alter myosin behavior in a concentration-dependent manner. MAVA has been shown to reduce the number of active myosin heads participating in crossbridge formation and force generation, while OM is recognized for prolonging motor attachment to act in filaments. Using these drugs as tools, we employ optical tweezers to understand how these drug-induced changes alter the coordination of cardiac myosin motors within the ensemble. By investigating motor stepping,force output, and binding dynamics in drug-treated samples, and comparing these with drug-free motor samples, we probe the adaptation mechanisms of cardiac myosin II to slowed motor detachment and removal of some motors from the network. Reducing motor crowding using MAVA enhanced ensemble force output, while OM stabilized attachment for smoother, more regulated force traces. These results indicate cardiac myosin coordination and force generation are uniquely sensitive to the number of motor heads available for force generation and actin binding kinetics, illustrating their adaptive force feedback loops as well as load sharing under different ensemble conditions.

Relational Format

Data Set

Comments

Data include: Raw out files of cardiac myosin ensemble optical trapping traces at different drug conditions given in the file or folder names. *.out files can be processed in Excel with the first column as time, second column as X position, third column as Y position, and force can be calculated from position by using the trap stiffness in the header of the file.

Recommended Citation

Alazzam, Omayma; Chowdhury, Md. Amzadul Hoque; and Stevens, Heath M., "Force-Feedback and Load Sharing Mechanisms in Cardiac Myosin II Ensembles Revealed by Motor-Specific Perturbations" (2026). Faculty and Student Publications. 66.
https://egrove.olemiss.edu/engineering_facpubs/66