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Computationally Modeled Cellular Response to the Extracellular Mechanical Environment

Scandling, Benjamin William
http://rave.ohiolink.edu/etdc/view?acc_num=osu1618918412753798

Abstract Details

2021, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
The human body is a complex mechanical environment that exposes cells to variations in both passive and active forces, where forces vary depending on tissue type, location, and function. Recent work has been done to analyze how the mechanical environment changes in different disease states and the effects of these changes on organ and cellular function. As a result, there are several well-known changes in in vitro cellular behavior in response to perturbations in the mechanical environment including: cell shape, size, phenotype, and differentiation. While other groups have begun to distinguish key components related to cell sensing of the mechanical environment, the exact mechanism remains poorly understood. The motor-clutch biophysical model describes cytoskeletal dynamics as a balance between substrate adhesion, myosin contractility, and actin polymerization. Initially, the model was hypothesized as a mechanism to explain cellular traction force generation and resultant actin flow. An initial computational formulation of the motor-clutch system demonstrated that it accurately predicts changes in neuronal cell behavior as a function of changes in extracellular substrate stiffness. Here we adapt the computational motor-clutch model to include external substrate motion as a means of simulating cyclic substrate deformation. We then use this adapted model to study the combined effect of cyclic substrate deformation and substrate stiffness on actin cytoskeleton organization and dynamics. The goal of this work was to demonstrate that the motor-clutch model can be used to predict and explain distinct cellular responses to applied cyclic strain. Furthermore, the adapted model allows for the study of experimental parameter spaces that are otherwise difficult to re-create experimentally. We found that the model predicts that applied cyclic stretch significantly impacts actin traction force generation and adhesion dynamics. Importantly, adhesion dynamics are finely controlled by substrate motion and control a cell's ability to generate traction along its substrate. We also found that the model precisely re-creates the distinct cellular reorientation response to cyclic stretch. Therefore, we propose the motor-clutch model as a mechanism for changes in cell morphology in response to the mechanical environment. The development of the adapted motor-clutch model not only reveals potentially novel cellular responses to changes in substrate compliance and deformation but can also be used to more closely study specific disease states that significantly alter the extracellular mechanical environment.
Keith Gooch, PhD (Advisor)
Aaron Trask, PhD (Committee Member)
Thomas Hund, PhD (Committee Member)
Seth Weinberg, PhD (Committee Member)
Biomedical Engineering
Mechanobiology; Computational Modeling; Cell Mechanics

Recommended Citations

Citations

  • Scandling, B. W. (2021). Computationally Modeled Cellular Response to the Extracellular Mechanical Environment [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1618918412753798

    APA Style (7th edition)

  • Scandling, Benjamin . Computationally Modeled Cellular Response to the Extracellular Mechanical Environment. 2021. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1618918412753798.

    MLA Style (8th edition)

  • Scandling, Benjamin . "Computationally Modeled Cellular Response to the Extracellular Mechanical Environment." Doctoral dissertation, Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1618918412753798

    Chicago Manual of Style (17th edition)

osu1618918412753798
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This open access ETD is published by The Ohio State University and OhioLINK.