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A COMPUTATIONAL STUDY OF CORTICAL CYTOSKELETAL REMODELING DURING CELL MORPHOGENESIS

thesis
posted on 24.11.2021, 04:57 authored by Jing LiJing Li

During development in both animals and plants, cell morphogenesis is fundamental to various aspects of cellular functions, including contractility, motility, and their ability to respond to physiological and mechanical stimuli. The cell cortex, consisting of actin and microtubule cytoskeletons, plays a critical role in the spatiotemporal regulation of cell morphogenesis. Remodeling of the cytoskeleton is responsible for a large fraction of morphogenetic processes. However, due to experimental limitations, the underlying mechanism of the remodeling of the cortical cytoskeleton remains elusive. These limitations can be overcome by computational models. We computationally investigated two systems: the actin cytoskeleton in animal cells and cortical microtubule arrays in plant cells. For the actin cytoskeleton, we implemented a well-established agent-based model consisting of inter-connected cylindrical segments representing actin filaments, actin crosslinking proteins, and molecular motors. We found that the active remodeling of actin networks is regulated by network connectivity as well as the dynamic behaviors of crosslinking proteins and motors. In addition, we demonstrated that the fragmentation (i.e., severing) and turnover of actin filaments mediate various clustering behaviors due to a balance between force generation and force relaxation. For microtubule arrays, we developed a coarse-grained model of microtubules based on the Gillespie algorithm. Using the model, we studied the self-organization of the cortical microtubule arrays in response to tensile stress. By implementing a cellular stress pattern and a constitutive relationship between stress and plus-end dynamics of microtubules, we were able to identify the most sensitive parameters that constitute dynamic instability and recapitulate a distinct morphological transverse band. We further validated the importance of branched nucleation and severing during bundle formation and network evolution. Overall, our results regarding the two cytoskeleton systems provide insights into understanding the precise control of cytoskeletal remodeling at subcellular scales as well as integrative molecular mechanisms underlying cell morphogenesis.

History

Degree Type

Doctor of Philosophy

Department

Biomedical Engineering

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Taeyoon Kim

Additional Committee Member 2

David M. Umulis

Additional Committee Member 3

Daniel B. Szymanski

Additional Committee Member 4

Daniel M. Suter