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Shawky, Joseph (2018) STRUCTURAL AND MOLECULAR REGULATORS OF EMBRYONIC TISSUE STIFFNESS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Embryonic development involves large scale tissue movements that construct complex three-dimensional tissue structures, governed by basic physical principles. Fine-grained control of mechanical properties and force production is critical to the successful placement of tissues and organs within the embryo. Cell generated forces and passive mechanical properties not only physically construct tissue structures, but may also provide feedback to instruct cell behavior, remodel extracellular matrix, and regulate intercellular adhesions.

Early embryos of the frog Xenopus laevis provide a dramatic example of these physical processes with rapidly changing mechanical properties, increasing in elastic modulus by six-fold to 80 Pascal over eight hours as germ layers and the central nervous system are formed. These physical changes coincide with emergence of complex anatomical structures, several rounds of cell division and remodeling of the cytoskeleton.

We analogize the mechanics of embryonic tissues to closed-cell foams to predict the influence of tissue architecture, cell size, and cell cortex on bulk tissue mechanics. The Cellular Solids Model (CSM) relates bulk stiffness of a solid-foam to the unit-size of individual cells, their microstructural organization, and their material properties. We confirmed the central assumption of the CSM, that tissue modulus does not depend on embedded structural elements by engineering and mechanically testing a tissue devoid of large coherent 3D structures. To test the role of cell size we generated large cells by arresting the cell cycle and generated small cells by inhibiting a developmentally regulated cell cycle inhibitor. Tissues with lower and higher cell density confirm predictions of the CSM but are only responsible for a modest 20% increase in stiffness from early to late neurulation. To modulate the composition and modulus of the "cell-wall" we enhanced and diminished cortical F-actin cross-linking. We found that levels of crosslinking regulate bulk tissue modulus. Our results indicate that large scale architecture and cell size are not likely to influence the bulk passive mechanical properties of early embryonic or progenitor tissues. Our findings suggest that regulation of F-actin cortical thickness, density, and integrity plays a central role in regulating the physical mechanics of embryonic multicellular tissues.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Shawky, Josephjhs35@pitt.edujhs35
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDavidson, Lancelad43@pitt.edulad430000-0002-2956-0437
Committee MemberRoy, Parthapar19@pitt.edupar190000-0002-4946-8531
Committee MemberWang, James H-C.wanghc@pitt.eduwanghc
Committee MemberFeinberg, Adamfeinberg@andrew.cmu.edun/a0000-0003-3338-5456
Date: 24 January 2018
Date Type: Publication
Defense Date: 5 September 2017
Approval Date: 24 January 2018
Submission Date: 21 October 2017
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 173
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: biomechanics, tissue architecture, tissue mechanics, cellular foam, germ layers, cell cycle, actin cross-linkers, actomyosin, morphogenesis, dissociation
Date Deposited: 24 Jan 2018 21:26
Last Modified: 24 Jan 2019 06:15


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