280671 Controlling Localized Xenopus Embryonic Tissue Migration in 3D Microenvironments

Friday, November 2, 2012: 10:00 AM
Cambria East (Westin )
Jiho Song, Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA

Controlling Localized Xenopus Embryonic Tissue Migration in 3D Microenvironments

Jiho Song1, YongTae Kim2, Melis Hazar1, Metin Sitti1, Philip R. LeDuc1, Lance A. Davidson3

1 Departments of Mechanical Engineering, Biomedical Engineering, and Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America, 2 Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3 Departments of Bioengineering and Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

            Cell migration and growth in multicellular tissues play important roles in morphogenesis, wound healing, and tumor metastasis. Many studies have focused on single cell mechanics and the response of motile cells to topological cues but little is known about the responses of migratory multicellular tissues to complex topological cues. Understanding cell and tissue migratory responses to well defined 3D substrates and the factors that regulate those dynamic responses are key to understanding the basic principles of cell sheet migration during embryonic development, which can contribute to fields from development to regenerative medicine. Presenting micropost arrays fabricated via MicroElectroMechanical Systems (MEMS) techniques can potentially provide advantages for studying the multicellular system response to substrate-based biophysical stimuli. Using micropost arrays with different diameters (e.g., different spacing gaps) and Xenopus laevis tissues cultured in a well-controlled microenvironment are studied for fundamental multicellular system responses to environmental cues. Our topographical controlled approach for cellular application enables us to achieve a high degree of control over micropost positioning and geometry via simple, accurate, and repeatable microfabrication processes.

            Here we introduce the methodology of constructing micropost array gradients to determine the multicellular system response to topology differences and showed that controlling 3D microenvironments could impact the shape, formation, and the rate of tissue cells migration. We have found a preferential direction of tissue migration over planar substrates yet there was a correlation between the rate of spreading when compared to micropost geometry. Cells in ectodermal Xenopus tissues migrated outward as cohesive sheets from their initial morphology. Post arrays slowed the cell movements over 20 hours. Sequential images from a representative time-lapse sequence showed that ectodermal tissues increased their surface area on flat substrates at a relatively rapid rate, but this movement was slower when the cells moved over the micropost arrays. As a control, ectodermal tissues migrated faster on entirely flat substrates. Tissues placed on flat-substrates at the margin of the post array, over the interface between flat-substrate and posts, and completely over the post array suggest topological cues may be used to shape tissue form. From these observations we hypothesized that tissue spreading might be limited by lateral forces from the posts which would oppose tissue movement. However, when we decreased the size of the posts the tissues spread more slowly suggesting that the surface area of the post array was one of the major limiting factors. Therefore, these approaches have lighted an important connection between cell mechanics and cell phenotype, particularly, the 2D nature of such techniques that inherently limit the extent to which 3D morphogenetic phenomena can be investigated although most tissue development is highly 3D.


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See more of this Session: Spatially Patterned Biomaterials
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