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Home > Mathematics and Science Textbooks > Biology, life sciences > Multicomponent Interfaces Modulate Neural Development in Vitro: (English)
Multicomponent Interfaces Modulate Neural Development in Vitro: (English)

Multicomponent Interfaces Modulate Neural Development in Vitro: (English)

          
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About the Book

Many neurological diseases and injuries result in the loss of functioning axonal/dendritic connections and neuronal degradation in the brain. Consequently, regeneration of the nervous system from those damages requires multi-step processes, including generation and survival of functional cells neurons and glia and the correct projection of axons and dendrites to form integrated circuits in the brain. Both processes are heavily regulated by the cellular microenvironments surrounding the cells. This dissertation presents a series of in vitro studies that interface microscale engineered structures with neural cells with the goal of investigating the spatial and temporal complexity of the cellular microenvironments during the neural development process. A set of methods were firstly introduced to pattern multiple bioactive cues, namely polylysine, L1 and N-cadherin, on a surface, to study how developing neurons integrate various guidance signals. Neurons exhibited a highly complex pattern of protein recognition on such surfaces. With somata residing on array of polylysine dots, dendrites extended exclusively on N-cadherin lines, while axons exhibited a very high degree of selectivity to L1 lines. This onset of L1 selectivity correlates with the establishment of intracellular L1 polarity, suggesting a functional outcome of neuron morphology polarization. The protein-micropatterned surfaces were then combined with a dual compartment microfluidic chamber into a new platform for the study of localized, sub-cellular signaling in axon guidance by tethered cues. N-cadherin patterned in the axon chamber was effective in both guiding and promoting motor axon outgrowth in the compartment. Selective inhibition of FGF receptor function in the axon but not the cell body, made possible using these chambers, reduced the rate of axon outgrowth while not affecting guidance along N-cadherin, indicating a role of local crosstalk between these pathways in helping axons navigate the complex extracellular environment. Moreover, the multicomponent system is also valuable to examine the role of cellular microenvironments in regulating neural stem cell (NSC) fate and function, which is another important aspect of neural development. The matrix molecule Fibronectin, co-patterned with cell-cell signaling ligands, Jagged1 or N-cadherin, was shown to spatially direct the localization of differentiated neurons according to the composition of protein patterns, suggesting a local environment mediated organization of NSC differentiation. Not only biochemical signals, but mechanical interaction with the surrounding extracellular matrix, or the intracellular contractility can also affect stem cell behavior. To dissect this aspect in NSC, elastomer pillar arrays were microfabricated and used to map subcellular forces generated by NSC, identifying new dynamics of force generation by these cells at different time scales, which is closely correlated with cells progression through differentiation. In summary, the presented studies exemplify the integration of current microfabrication technique with neurobiology research focusing on cell-environment interactions during neural development processes. The qualitative and quantitative guidelines established in these studies may lead to improved design of next generation of investigative and therapeutic devices for the nervous system.


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Product Details
  • ISBN-13: 9781243727862
  • Publisher: Proquest, Umi Dissertation Publishing
  • Publisher Imprint: Proquest, Umi Dissertation Publishing
  • Height: 246 mm
  • No of Pages: 162
  • Series Title: English
  • Weight: 299 gr
  • ISBN-10: 1243727861
  • Publisher Date: 01 Sep 2011
  • Binding: Paperback
  • Language: English
  • Returnable: N
  • Spine Width: 9 mm
  • Width: 189 mm


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Multicomponent Interfaces Modulate Neural Development in Vitro: (English)
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