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1.
Biomaterials ; 183: 54-66, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30149230

RESUMO

Duchenne Muscular Dystrophy (DMD) is a fatal genetic disorder currently having no cure. Here we report that culture substrates patterned with nanogrooves and functionalized with Matrigel (or laminin) present an engineered cell microenvironment to allow myotubes derived from non-diseased, less-affected DMD, and severely-affected DMD human induced pluripotent stem cells (hiPSCs) to exhibit prominent differences in alignment and orientation, providing a sensitive phenotypic biomarker to potentially facilitate DMD drug development and early diagnosis. We discovered that myotubes differentiated from myogenic progenitors derived from non-diseased hiPSCs align nearly perpendicular to nanogrooves, a phenomenon not reported previously. We further found that myotubes derived from hiPSCs of a dystrophin-null DMD patient orient randomly, and those from hiPSCs of a patient carrying partially functional dystrophin align approximately 14° off the alignment direction of non-diseased myotubes. Substrates engineered with micron-scale grooves and/or cell adhesion molecules only interacting with integrins all guide parallel myotube alignment to grooves and lose the ability to distinguish different cell types. Disruption of the interaction between the Dystrophin-Associated-Protein-Complex (DAPC) and laminin by heparin or anti-α-dystroglycan antibody IIH6 disenables myotubes to align perpendicular to nanogrooves, suggesting that this phenotype is controlled by the DAPC-mediated cytoskeleton-extracellular matrix linkage.


Assuntos
Fibras Musculares Esqueléticas/fisiologia , Distrofia Muscular de Duchenne/diagnóstico , Nanoestruturas/química , Biomarcadores , Diferenciação Celular , Células Cultivadas , Microambiente Celular , Colágeno/metabolismo , Citoesqueleto/metabolismo , Combinação de Medicamentos , Distrofina/metabolismo , Complexo de Proteínas Associadas Distrofina/metabolismo , Matriz Extracelular/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/fisiologia , Laminina/metabolismo , Desenvolvimento Muscular , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Mioblastos/metabolismo , Mioblastos/patologia , Fenótipo , Proteoglicanas/metabolismo
2.
Nano Lett ; 14(5): 2741-6, 2014 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-24734877

RESUMO

Graphene's unique optoelectronic properties have been exploited for many photonic applications. Here, we demonstrate a single graphene-based device that simultaneously provides efficient optical modulation and photodetection. The graphene device is integrated on a silicon waveguide and is tunable with a graphene gate to achieve a near-infrared photodetection responsivity of 57 mA/W and modulation depth of 64% with GHz bandwidth. Simultaneous modulation of photocurrent and optical transmission has been achieved, which may lead to unprecedented optoelectronic applications.

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