摘要:

Insight, innovation, integrationAltered intracellular Ca2+signaling has been linked to many muscle diseases. Here we provide evidence to show that genetic mutations in ryanodine receptor leads to impaired inter-molecular interactions among the Ca2+release channels, which is associated with the pharmacogenetic skeletal muscle disorder—malignant hyperthermia. Our data suggests that in addition to defects in individual receptor components, failed maintenance of inter-molecular coupling may be a new pathophysiological mechanism of human diseases.

ISSN:1757-9694    

DOI:10.1039/b907812f

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationHeterogeneity of stem cell populations is a well-known but poorly characterized phenomenon. Here, we provide single-cell transcript profiles of individual human embryonic stem cells that clearly identify cellular heterogeneity in these populations and identify novel cell types. This transcript analysis is presented at a level of depth and resolution not attainable by other methods. None of the insights in this study would have been possible with standard population-level transcript analysis or single-cell FACS analysis of known cell surface markers. Only by developing robust single-cell transcript profiling techniques and applying these to established stem cell differentiation paradigms were we able to deconstruct complex populations of cells into their component parts.

ISSN:1757-9694    

DOI:10.1039/b908276j

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationMechanical forces play crucial roles in regulating cellular functions. However, it remains elusive on how cells perceive these mechanical cues and transduce them into biochemical signals. With the development of genetically-encoded biosensors based on fluorescence resonance energy transfer (FRET), it is possible to quantify the live-cell molecular activities in real time at subcellular levels when cells are subjected to mechanical stimulation. This article reviews the research on the integration of cutting-edge FRET biosensors and mechanobiology, with a special emphasis on the innovative imaging techniques in live cells. The integration of FRET and mechanobiology should advance our systematic and insightful understanding on how cells sense and adapt to different mechanical environments to yield concerted biological responses in a living organism.

ISSN:1757-9694    

DOI:10.1039/b913093b

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Jungkyu KimJungkyu Kim received his PhD in Biomedical Engineering from University of Utah in 2009. He has been working in the area of microfluidics fabrication technique, microfluidic sample preparation and Lab-on-a-chip development for personalized medicine and bacteria detection. He is currently a postdoc researcher in Electrical Engineering at University of California, Berkeley.

ISSN:1757-9694    

DOI:10.1039/b905844c

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationMicroenvironmental conditions impact tumourigenesis, but the underlying mechanisms remain poorly understood. We have developed and utilised a simple and adaptable micropatterning technology with parylene peel-off templates to spatiotemporally control the cell–cell interactions between tumour cells. Our technology enables the reproducible patterning of biomaterials uniformly across large chip surface areas, allowing for the quantification of protein secretions by tumour cells in the presence or absence of cell–cell contact. Our results indicate that cell–cell interactions synergistically regulate the expression of pro-angiogenic factors in various cancer cell lines and induce the angiogenic switch independent of other microenvironmental cues, such as hypoxia. Our developed Peel-Off array chips have the potential to enhance the understanding of the role of cell–cell interactions in tumour angiogenesis.

ISSN:1757-9694    

DOI:10.1039/b908036h

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationAdipocytes and insulin-producing pancreatic β-cells have key roles in the development of type 2 diabetes (T2D). However, the mechanisms involved are still unclear. Levitation technology provides a solution in T2D related research, allowing for real-time single-cell and cell–cell communication studies, in the sub-microlitre volume range. The “contactless” sample handling outweighs the issues associated with most miniaturization techniques, such as sample loss and contamination, and sorption processes on container walls, leading to better detection limits and accuracy. In addition, performing airborne science at the single/few-cell level will allow for the use of cells obtained from human biopsies, reducing the need for laboratory animals.

ISSN:1757-9694    

DOI:10.1039/b907834g

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationMany biological processes occur on a timescale of milliseconds. Investigations at the single-molecule level whilst retaining functionality is difficult to achieve with existing technology. Previously, functional imaging using fluorescent proteins was limited to events over a timescale of tens of milliseconds, and the observation of slow, membrane processes. Here we report an innovative imaging hardware and software package permitting detection and quantification of fluorescent proteins in single cells at ∼500 frames per second. We have integrated this technology towards addressing outstanding biological questions by demonstrating its usein vitroon several different fluorescent proteins at the single-molecule level and reporting preliminary data for its application to live-cell imaging. This non-invasive imaging package will provide unprecedented insight into fastin vivoprocesses.

ISSN:1757-9694    

DOI:10.1039/b907837a

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationCell and tissue fate is intimately linked to the biochemistry and physical properties of their microenvironments (including mesenchyme, stroma and stem cell niches), yet no tools were available to probe how cell-generated tensile forces physically alter the properties of 3D extracellular matrix. FRET-labeled fibronectin is exploited as a mechanical strain sensor to monitor time-dependent changes of either tissue-mimetic 3D, ECM scaffolds reseeded with cells or of the newly assembled matrix fibrils. Thisin situmethod is versatile, since cells, provided exogenously with FRET-fibronectin, typically co-assembled it into their ECM fibers. Probing how environmental conditions regulate cell-mediated stretching of ECM fibers is physiologically significant because stretching alters fiber rigidity and the presentation of molecular and cellular recognition sites (mechanotransduction).

ISSN:1757-9694    

DOI:10.1039/b914996a

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationWe developed a microfluidic cell patterning method to form patterned spheroids of multiple cell types. Our technique is unique in that the 3D co-culture spheroids can be constructed where initial positions of different cell types can be controlled. This capability led to the new insight that the initial position of the cells can dictate the final organization of the cell constructs. The importance of this is seen by the patterned differentiation of ES cells which may be utilized for tissue engineering purposes or used as a platform to study embryonic development. These capabilities and insights provide new tools and concepts to investigate development and tissue organization.

ISSN:1757-9694    

DOI:10.1039/b915965g

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

Insight, innovation, integrationThe magnitude of a single dimensionless group of biological and physical (flow) parameters is shown to govern the spread of virus infections and the work is the first to show how fluid flows may couple with virus production to impact spatial–temporal patterns of infection spread. Theory is developed to support an integrative understanding of how essential physical and biological processes combine to influence the dynamics of infection spread

ISSN:1757-9694    

DOI:10.1039/b908197f

出版商:RSC    

年代:2009

数据来源: RSC