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Exploring Super-Loading Mechanisms of the Motor-Clutch Model

Fernandes, Ketan Earl
http://rave.ohiolink.edu/etdc/view?acc_num=osu1641492108183234

Abstract Details

2022, Master of Science, Ohio State University, Biomedical Engineering.
The motor-clutch model is a mechanosensing model that enables cells to probe their extracellular environment via interactions between myosin motors and molecular clutches through actin filaments. While two substrate-dependent behaviors have emerged from this model, there has been a third type of behavior that has also been discovered, characterized by high molecular clutch engagement with actin and prolonged bond lifetimes, which was described as super-loading. While it has been theorized that it can occur on super soft substrates in the absence of clutch reinforcement mechanisms, it can also occur on intermediate to stiff substrates when clutches undergo reinforcement, as shown from previous studies. In this study, the mechanisms influencing super-loading behavior were examined focusing exclusively on intermediate to stiff substrates through analysis of the effects of the initial binding rate, the reinforcement rate, and changes in the clutch-to-motor (CMR) ratio. It was found that the initial binding rate is able to influence what types of behaviors the motor-clutch model can exhibit and can even prevent certain behaviors from occurring, regardless of the incorporation of clutch reinforcement. While reinforcement rates were able to shift cell traction, spreading velocity, and clutch engagement as well, they did so mostly on intermediate to stiff substrates. Because reinforcement rates had to be increased 10-fold from the base parameter values to induce super-loading on stiff substrates, it was additionally sought to determine if modifying the CMR could allow for super-loading to occur under minimally increased rates of reinforcement and initial binding rates. Ultimately, super-loading could be observed on both intermediate and stiff substrates at higher CMR ratios and in most initial binding rates. In cases where the initial binding rate was increased, higher CMRs could achieve a near-stalled system, characterized by super-loading on all substrate stiffnesses and minimal to no increases from the initial binding rate. These findings can help determine can provide insight into which parameters are the most influential during cell development and spreading dynamics particularly during biological processes such as integrin sensing and mechanotransduction.
Seth Weinberg (Committee Member)
Keith Gooch (Advisor)
91 p.
Biomedical Engineering; Biomedical Research
cell mechanobiology, motor-clutch model, cell spreading, clutch reinforcement mechanisms

Recommended Citations

Citations

  • Fernandes, K. E. (2022). Exploring Super-Loading Mechanisms of the Motor-Clutch Model [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1641492108183234

    APA Style (7th edition)

  • Fernandes, Ketan. Exploring Super-Loading Mechanisms of the Motor-Clutch Model. 2022. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1641492108183234.

    MLA Style (8th edition)

  • Fernandes, Ketan. "Exploring Super-Loading Mechanisms of the Motor-Clutch Model." Master's thesis, Ohio State University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=osu1641492108183234

    Chicago Manual of Style (17th edition)

osu1641492108183234
108
© 2022, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.