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Motor Occupancy Defines Emergent Mechanical States in Cardiac Myosin Ensembles
Omayma Y Alazzam1, Md Amzadul Hoque Chowdhury1, Heath M Stevens1
1Department of Biomedical Engineering, University of Mississippi, University, MS, USA.
Biorxiv : the Preprint Server for Biology
|July 29, 2026
Summary
Cardiac myosin ensembles achieve maximal force at intermediate motor occupancy, adapting to changes via mechanical feedback. This balance between occupancy and coordination is key, not just motor number.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Mechanics
Background:
- Myosin II motor ensembles generate force collectively, but sensing motor occupancy and coordinating force is not well understood.
- Ensemble force may depend on an optimal balance between motor occupancy and mechanical coordination, not solely motor number.
Purpose of the Study:
- To investigate how cardiac myosin ensembles sense changes in motor occupancy and coordinate force generation.
- To explore the relationship between effective motor occupancy and ensemble force production.
Main Methods:
- Reconstitution of cardiac myosin ensembles.
- Perturbation of motor occupancy using omecamtiv mecarbil (OM) and mavacamten (MAVA).
- Optical trapping measurements of myosin ensembles.
Main Results:
- Force generation depended on myosin concentration and drug perturbation.
- OM and Mavacamten showed occupancy-dependent effects on force and dynamics.
- Maximal force generation occurred at intermediate effective motor occupancy.
Conclusions:
- Cardiac myosin ensembles operate on an occupancy-coordination landscape.
- Ensembles collectively sense and adapt to their mechanical state through feedback.
- Understanding this balance is crucial for cardiac function.
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