23 research outputs found

    Peptide Arrays Identify Isoform-Selective Substrates for Profiling Endogenous Lysine Deacetylase Activity

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    A cetylation of lysine is a post-translational modifi-cation involved inmany eukaryotic cellular pro-cesses (1). Though most commonly associated with histone proteins (2), a recent proteomic study by Mann and colleagues identified nearly 2,000 proteins in acetylated form and showed that this modification is used globally in regulating cell function (3). This recogni-tion hasmotivated a renaming of the histone acetyltrans-ferase (HAT) and histone deacetylase (HDAC) enzymes to reflect their broader roles [now the lysine acetyltrans-ferases (KATs) and the lysine deacetylases (KDACs) (4)] and has highlighted our limited understanding of the functions of the individual enzymes responsible for achieving andmaintaining acetylation states. A significant effort is now directed at understanding the differential roles that the 18 human KDAC isoforms play in regulating cell behavior (5āˆ’8). These studies re

    Cellular signaling

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    The mechanism by which cells receive and respond to stimuli is known as cell signaling. By understanding the fundamentals of cell signaling, tissue engineers can better direct cell behavior. This chapter outlines the paradigm of cell signaling, from signal initiation to signal transduction to gene activation. The main types of signals, receptors, and the machinery for gene activation are described and specific signaling cascades relevant to tissue engineering are outlined. For example, the G-protein-coupled receptors and the receptor tyrosine kinases are detailed, as are the TGF-Ɵ superfamily, Wnt signaling, Rho kinase signaling, NF-?B signaling, and vitamin D signaling. The complexity of cellular signaling is underlined with examples of where it deviates from the classical descriptions of these pathways. Throughout this chapter, various means for tissue engineers to exploit these pathways to direct cell behavior are revealed. And finally, a future perspective about how tissue engineering will continue to benefit from advances in cell signaling is given

    Biomechanical, biophysical and biochemical modulators of cytoskeletal remodelling and emergent stem cell lineage commitment

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    This review highlights the biomechanical, biophysical, and biochemical modulators of cytoskeletal remodeling during tissue neogenesis in early development and postnatal healing for targeted tissue regeneration and regenerative medicineĀ applications

    Mechanochemical functionalization of disulfide linked hydrogels

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    Si-C linked oligo(ethylene glycol) layers in silicon-based photonic crystals: Optimization for implantable optical materials

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    Abstract Porous silicon has shown potential for various applications in biology and medicine, which require that the material (1) remain stable for the length of the intended application and (2) resist non-specific adsorption of proteins. Here we explore the efficacy of short oligo(ethylene glycol) moieties incorporated into organic layers via two separate strategies in achieving these aims. In the first strategy the porous silicon structure was modified in a single step via hydrosilylation of a-oligo(ethylene glycol)-o-alkenes containing three or six ethylene glycol units. The second strategy employs two steps: (1) hydrosilylation of succinimidyl-10-undecenoate and (2) coupling of an amino hexa(ethylene glycol) species. The porous silicon photonic crystals modified by the two-step strategy displayed greater stability relative to the single step procedure when exposed to conditions of physiological temperature and pH. Both strategies produced layers that resist non-specific adsorption of proteins as determined with fluorescently labelled bovine serum albumin. The antifouling behaviour and greater stability to physiological conditions provided by this chemistry enhances the suitability of porous silicon for biomaterials applications.

    Influence of Biophysical Parameters on Maintaining the Mesenchymal Stem Cell Phenotype

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    The maintenance of the mesenchymal stem cell (MSC) phenotype in vivo is influenced by the precise orchestration of biochemical and biophysical signals in the stem cell ā€œnicheā€. However, when MSCs are removed from the body and expanded in vitro, there is a loss of multipotency. Here, we employ micropatterned hydrogels to explore how biophysical cues influence the retention of MSC multipotency marker expression. At the single-cell level, soft substrates and patterns that restrict spreading and cytoskeletal tension help maintain the expression of MSC markers. When MSCs are patterned in multicellular geometries, both high cell density and regions of low tension within the pattern are shown to assist the maintenance of multipotency. Combining experiment and simulation along with cytoskeleton disrupting agents reveals spatial patterns of cytoskeletal tension in multicellular architectures that guides the expression of markers associated with MSC multipotency. These findings uncover a relationship between multiple biophysical parameters in maintaining the MSC phenotype, which may shed light on the structure of the MSC ā€œnicheā€ and prove useful in guiding the selection of in vitro expansion materials for regenerative therapies
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