ORCID Profile
0000-0003-1642-5380
Current Organisation
University of California, San Diego
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Publisher: Oxford University Press (OUP)
Date: 11-2013
DOI: 10.1002/STEM.1490
Abstract: Human mesenchymal stem cell (hMSC) proliferation, migration, and differentiation have all been linked to extracellular matrix stiffness, yet the signaling pathway(s) that are necessary for mechanotransduction remain unproven. Vinculin has been implicated as a mechanosensor in vitro, but here we demonstrate its ability to also regulate stem cell behavior, including hMSC differentiation. RNA interference-mediated vinculin knockdown significantly decreased stiffness-induced MyoD, a muscle transcription factor, but not Runx2, an osteoblast transcription factor, and impaired stiffness-mediated migration. A kinase binding accessibility screen predicted a cryptic MAPK1 signaling site in vinculin which could regulate these behaviors. Indeed, reintroduction of vinculin domains into knocked down cells indicated that MAPK1 binding site-containing vinculin constructs were necessary for hMSC expression of MyoD. Vinculin knockdown does not appear to interfere with focal adhesion assembly, significantly alter adhesive properties, or diminish cell traction force generation, indicating that its knockdown only adversely affected MAPK1 signaling. These data provide some of the first evidence that a force-sensitive adhesion protein can regulate stem cell fate.
Publisher: Oxford University Press (OUP)
Date: 2013
DOI: 10.1039/C3IB40078F
Publisher: American Association for the Advancement of Science (AAAS)
Date: 10-04-2009
Abstract: Topobiology posits that morphogenesis is driven by differential adhesive interactions among heterogeneous cell populations. This paradigm has been revised to include force-dependent molecular switches, cell and tissue tension, and reciprocal interactions with the microenvironment. It is now appreciated that tissue development is executed through conserved decision-making modules that operate on multiple length scales from the molecular and subcellular level through to the cell and tissue level and that these regulatory mechanisms specify cell and tissue fate by modifying the context of cellular signaling and gene expression. Here, we discuss the origin of these decision-making modules and illustrate how emergent properties of adhesion-directed multicellular structures sculpt the tissue, promote its functionality, and maintain its homeostasis through spatial segregation and organization of anchored proteins and secreted factors and through emergent properties of tissues, including tension fields and energy optimization.
Publisher: Wiley
Date: 21-04-2016
DOI: 10.1002/JOR.23256
Publisher: Wiley
Date: 28-04-2014
Publisher: Wiley
Date: 28-02-2013
Publisher: Elsevier BV
Date: 10-2012
Publisher: Springer Berlin Heidelberg
Date: 2013
Publisher: Elsevier BV
Date: 11-2013
Publisher: Elsevier BV
Date: 03-2012
Publisher: Springer Science and Business Media LLC
Date: 10-08-2014
DOI: 10.1038/NMAT4051
Publisher: Proceedings of the National Academy of Sciences
Date: 15-05-2017
Abstract: Mechanobiology is receiving an increasing amount of focus, but the mechanics of cell-substrate behavior are often neglected in cell biology. As such, novel materials and systems that are simple to build and share in a nonengineering laboratory are sorely needed. We have fabricated gradient hydrogels with continuous linear gradients above and below the durotactic threshold, making it possible to pinpoint optimal stiffness values for a wide range of biological phenomena without the confounding effects of durotaxis. This system has the potential for wide adoption in the cell biology community because of its ease of fabrication, simple material ingredients, and wide gradient possibilities in a single well.
Publisher: American Chemical Society (ACS)
Date: 23-02-2011
DOI: 10.1021/NN102455Z
Abstract: Nature has the exquisite ability to design specific surface patterns and topologies on both the macro- and nanolength scales that relate to precise functions. Following a biomimetic approach, we have engineered fully synthetic nanoparticles that are able to self-organize their surface into controlled domains. We focused on polymeric vesicles or "polymersomes" enclosed membranes formed via self-assembly of hiphilic block copolymers in water. Exploiting the intrinsic thermodynamic tendency of dissimilar polymers to undergo phase separation, we mixed different vesicle-forming block copolymers in various proportions in order to obtain a wide range of polymersomes with differing surface domains. Using a combination of confocal laser scanning microscopy studies of micrometer-sized polymersomes, and electron microscopy, atomic force microscopy, and fluorescence spectroscopy on nanometer-sized polymersomes, we find that the domains exhibit similar shapes on both the micro- and nanolength scales, with dimensions that are linearly proportional to the vesicle diameter. Finally, we demonstrate that such control over the surface "patchiness" of these polymersomes determines their cell internalization kinetics for live cells.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.BIOMATERIALS.2015.03.016
Abstract: Development of stem cell delivery system with ability of control over mutilineage differentiation and improved engraft efficiency is imperative in regenerative medicine. We herein report transfer st ing of human mesenchymal stem cells (hMSCs) patches using thermally expandable hydrogels with tunable cell-adhesive properties. The hydrogels were prepared from functionalized four arm copolymer of Tetronic(®), and the cell adhesion on the hydrogel was modulated by incorporation of fibronectin (FN) or cell-adhesive peptide (RGD). The resulting hydrogels showed spontaneous expansion in size within 10 min in response to the temperature reduction from 37 to 4°C. The adhesion and proliferation of hMSCs on FN-hydrogels were positively tunable in proportion to the amount of FN within hydrogels with complete monolayer of hMSCs (hMSC patch) being successfully achieved. The hMSC patch on the hydrogel was faced to the target substrate, which was then easily detached and re-attached to the target when the temperature was reduced from 37°C up to 4°C. We found that the transfer st ing of cell patch was facilitated at lower temperature of 4°C relative to 25°C, with the use of thinner hydrogels (0.5 mm in thickness relatively to 1.0 or 1.5 mm) and longer transfer time (>15 min). Notably, the hMSC patch was simply transferred from the hydrogel to the subcutaneous mouse skin tissue within 15 min with cold saline solution being dropped to the hydrogel. The hMSC patch following osteogenic or adipogenic commitment was also achieved with long-term culture of hMSCs on the hydrogel, which was successfully detached to the target surface. These results suggest that the hydrogels with thermally expandable and tunable cell-adhesive properties may serve as a universal substrate to harvest hMSC patch in a reliable and effective manner, which could potentially be utilized in many cell-sheet based therapeutic applications.
Location: United States of America
Start Date: 2016
End Date: 2018
Funder: National Health and Medical Research Council
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