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Title page for ETD etd-11082018-173400


Type of Document Dissertation
Author Fenix, Aidan Mandy
Author's Email Address aidan.m.fenix@vanderbilt.edu
URN etd-11082018-173400
Title Constructing Contractile Ensembles: How Cells Build Units of Force Generation
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
David M. Miller Committee Chair
Dylan T. Burnette Committee Member
Irina Kaverina Committee Member
Jason R. Becker Committee Member
Matthew J. Tyska Committee Member
Keywords
  • Myosin II
  • Actin
  • Cardiomyocytes
  • Sarcomeres
Date of Defense 2018-10-09
Availability unrestricted
Abstract
Force generation at the cellular level is critical for eukaryotic development, homeostasis, and the progression of force dependent diseases such as cancer. Molecular motors coordinate with cytoskeletal elements, such as actin filaments, to drive force dependent processes such as cell migration, cell division, and muscle contraction. These seemingly diverse processes are all driven by forces generated by the same contractile machinery: actin and myosin II. Despite centuries of research into how cells and tissues generate the forces required for life, how cells build the contractile machinery powering diverse cellular functions is poorly understood. Here, we use two seemingly different experimental systems to study how diverse cell types assemble contractile ensembles. First, we use crawling and dividing cells to demonstrate how cancer cells build contractile ensembles. Using experimental paradigms established in this work, we then use human iPSC-derived cardiac myocytes to demonstrate how heart cells responsible for the beating of the heart assemble their own (related) contractile ensembles.
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