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Biophysical and gene expression change in living cells by force-induced mechanotransduction
Get PDFWithin the past decade, there has been abounding scientific evidences supporting the notion that mechanical forces are crucial in regulating the physiologic functions of cells and tissues. The importance of engineering principles in studying the biological behavior of cells is no longer in question. Instead, much research is now focused on how mechanical forces are transduced into biochemical activities and biological responses at the cellular and molecular level - a process known as mechanotransduction. This work uses both engineering and biological principles to investigate the different biophysical and gene expression changes of individual cells in response to exogenous forces. We attempt to unravel the mechanism at which forces are transmitted from the apical surface of the cell in to the nucleus.
The work presented here provides the first unequivocal evidence that a local surface force can directly alter nuclear functions without intermediate biochemical cascades. We show that a local dynamic force via integrins results in direct displacements of coilin and SMN proteins in Cajal bodies and direct dissociation of coilin-SMN associated complexes. Fluorescence resonance energy transfer changes of coilin-SMN depend on force magnitude, an intact F-actin, cytoskeletal tension, Lamin A/C, or substrate rigidity. Other protein pairs in Cajal bodies exhibit different magnitudes of fluorescence resonance energy transfer. Dynamic cyclic force induces tiny phase lags between various protein pairs in Cajal bodies, suggesting viscoelastic interactions between them. These findings demonstrate that dynamic force-induced direct structural changes of protein complexes in Cajal bodies may represent a unique mechanism of mechanotransduction that impacts on nuclear functions involved in gene expression.
We further extend our study to mouse embryonic stem cells (ESCs). Increasing evidence suggests that mechanical factors play a critical role in fate decisions of stem cells. We demonstrate that forces transmitted through different natural extracellular matrix proteins or cell-cell adhesion molecules such as fibronectin, laminin or E-cadherin, have different effects on cell spreading, cell stiffness, Oct3/4 gene expression, and cell proliferation rate. Surprisingly, it was also observed that mouse ESCs do not stiffen when substrate stiffness increases. These cells do not increase spreading on more-rigid substrates either. However, ESCs do increase their basal tractions as substrate stiffness increases. ESCs therefore exhibit mechanical behaviors distinct from those of mesenchymal stem cells and of terminally differentiated cells, and decouple its apical cell stiffness from its basal tractional stresses during the substrate rigidity response. We further elucidate how mechanical forces influence the differentiation of ESCs into spatially organized endoderm, mesoderm, and ectoderm germ layers. ESCs cultured within 3D soft fibrin gels in the absence of Leukemia Inhibitory Factor (LIF) promotes in vivo tissue morphogenesis during vertebrate gastrulation. The results presented demonstrate that mechanical forces play different roles in different force transduction pathways to shape early embryogenesis.Item withdrawn by Mark Zulauf ([email protected]) on 2013-04-15T18:47:34Z
Item was in collections:
University of Illinois Theses & Dissertations (ID: 1)
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license.txt: 4060 bytes, checksum: 76863f98ad7a8e8d6e99b96962c6d380 (MD5)Item marked as restricted to the 'Administrator' Group (id=1) by Seth Robbins ([email protected]) on 2013-05-28T19:21:42Z
Item is restricted until 2015-05-28T19:21:22ZRestriction data tranferred 2014-07-01T11:16:50-05:00
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Rapid Rac GTP-ASE activation in live cells by mechanical stress is independent of Src
No full textIt is well-known that mechanical forces are crucial in regulating functions of every tissue and organ in a human body. However, it remains unclear how mechanical forces are transduced into biochemical activities and biological responses at the cellular and molecular level. Using the magnetic twisting cytometry technique, we applied local mechanical stresses to living human airway smooth muscle cells with a magnetic bead bound to the cell surface via transmembrane adhesion molecule integrins. The temporal and spatial activation of Rac, a small guanosine triphosphatase, was quantified using a fluorescent resonance energy transfer (FRET) method that measures changes in Rac activity in response to mechanical stresses by quantifying intensity ratios of ECFP (enhanced cyan fluorescent protein as a donor) and YPet (a variant yellow fluorescent protein as an acceptor) of the Rac biosensor. The applied stress induced rapid activation (less than 300 ms) of Rac at the cell periphery. In contrast, platelet derived growth factor (PDGF) induced Rac activation at a much later time (>30 sec). It is known that PDGF-induced Rac activation depends on Src activity. There was no stress-induced Rac activation when a mutant form of the Rac biosensor (RacN17) was transfected or when the magnetic bead was coated with transferrin or with poly-L-lysine. Surprisingly, pre-treatment of the cells with specific Src inhibitor PP1 or knocking-out Src gene had no effects on stress-induced Rac activation. In addition, eliminating lipid rafts through extraction of cholesterol from the plasma membrane did not prevent stress-induced Rac activation, suggesting a raft-independent mechanism in governing the Rac activation upon mechanical stimulation. Further evidence indicates that Rac activation by stress depends on the magnitudes of the applied stress and cytoskeletal integrity. Our results suggest that Rac activation by mechanical forces is rapid, direct and does not depend on Src activation. These findings suggest that signaling pathways of mechanical forces might be fundamentally different from those of growth factors.Item withdrawn by Mark Zulauf ([email protected]) on 2009-12-02T21:53:17Z
Item was in collections:
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Item is restricted until 2012-01-06T16:42:19ZItem reinstated by Sarah Shreeves ([email protected]) on 2012-01-07T11:00:09Z
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University of Illinois Dissertations and Theses (ID: 204)
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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