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Identifying Essential Mechanisms for Cortical Actomyosin Contractions with Computational Modeling

Miller, Callie Johnson (2014) Identifying Essential Mechanisms for Cortical Actomyosin Contractions with Computational Modeling. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The success of embryogenesis requires coordinated cell-cell signaling, tissue patterning, and morphogenetic movements. In order to understand how birth defects such as spin bifid a occur, we must understand how signaling and patterning integrate mechanically to drive morphogenetic movements. Although there are many different scales to consider (molecular, cellular or tissue), this dissertation is unique in its attempt to bridge molecular biophysics to cell- and tissue-scale biomechanics. On the molecular level, filamentous actin (F-actin) and non-muscle myosin II (NMM II) motors are cytoskeletal proteins responsible for cell motility and shape change. Currently, there are no techniques for measuring in vivo forces generated by actomyosin. In order to gain a better understanding of the behavior of actomyosin in vivo, we have developed theoretical models, beginning with a simple rotational model for actomyosin, and extended the theory to a simple sliding filament system. Based on the results and intuition gained from these simple models, we developed a 2D model where we can study the emergent morphology of the filaments and motors. In vivo, we observe actomyosin punctuated contractions which initiate from a quiescent background of F-actin to flow into a region of high intensity and disassemble, returning to baseline levels. Previous research showed the correlation between the locations of these punctuated contractions and the resultant cell shape change during development. The 2D model allows us to explore the kinematics of F-actin arrays and the dynamics of their force production as we vary biophysical parameters. We can also test the model results against in vitro observations of purified actin and myosin. Although still simplified, our model has set the groundwork for future studies on the role of actin binding proteins in actomyosin dynamics, simulating the role of actomyosin in cell shape change, and making comparative measurements for experimental studies of purified cytoskeletal actomyosin.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Miller, Callie Johnsoncaj30@pitt.eduCAJ30
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDavidson, Lance Alad43@pitt.eduLAD43
Committee MemberErmentrout, Bardbard@pitt.eduBARD
Committee MemberShroff, Sanjeev G
Committee MemberAbramowitch, Steven Dsdast9@pitt.eduSDAST9
Date: 19 September 2014
Date Type: Publication
Defense Date: 11 July 2014
Approval Date: 19 September 2014
Submission Date: 27 June 2014
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 248
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: developmental biology, Monte Carlo methods, computational simulations, actomyosin, mechanics
Date Deposited: 19 Sep 2014 18:15
Last Modified: 15 Nov 2016 14:21

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