Date of Award
1-1-2024
Document Type
Dissertation
Degree Name
Ph.D. in Engineering Science
First Advisor
Nikki D. Rienemann
Second Advisor
Adam Smith
Third Advisor
Adam Smith
Relational Format
dissertation/thesis
Abstract
This dissertation delves into the dynamics of myosin II motors within actomyosin networks, emphasizing their crucial role in muscle functionality and the broader implications for cardiovascular health. Given the critical involvement of myosin II in conditions such as hypertrophic cardiomyopathy (HCM) and heart failure, this research presented here is important for understanding such diseases at the molecular level. Through the use of fluorescence microscopy and optical tweezers, the study reveals novel insights into how myosin II generates force and coordinates within myosin ensembles—a key to grasping the mechanics of muscle contraction. Specifically, this work aimed to unravel the mechanisms of myosin II functionality in actomyosin ensembles and to assess how variations in the dynamics of motor proteins affect force production. We leveraged a novel assay that probes the complex interactions of myosin II within hierarchical structures with mechanical compliancy, allowing for more native-like measurements of force generation and the analysis of myosin ensemble behavior. Results reveal the significant impact of environmental stiffness and the number of engaged motors on the behavior of myosin II ensembles. The study sheds light on a sophisticated system of sensory force feedback among myosin motors, showing that force production results from the collective dynamics of the ensemble, rather than from the actions of individual motors. Additionally, it was discovered that changes in the environmental context and structure of the ensemble can significantly alter force output. This work advances understanding of muscle mechanics at the molecular level and how emergent biophysical properties of the cytoskeleton rely on intricate feedback loops. By elucidating the principles of force generation and coordination within actomyosin networks, this research sets the stage for future studies aimed at understanding the details of the feedback loops, influences of mechanical environments on intracellular crosstalk, and creating targeted treatments for cardiovascular conditions linked to malfunctioning myosin II motors.
Recommended Citation
Alazzam, Omayma, "Elucidating the Mechanisms of Myosin II Force Feedback and Coordination in Actomyosin Ensembles" (2024). Electronic Theses and Dissertations. 2785.
https://egrove.olemiss.edu/etd/2785