Subcellular positioning of small molecules

Takayama, Shuichi; Ostuni, Emanuele; LeDuc, Philip; Naruse, Keiji; Ingber, Donald E.; Whitesides, George M.

doi:10.1038/35082637

Cited by 512 publications

(364 citation statements)

References 11 publications

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“…The authors demonstrated the selective loading of dendrites with Calcein AM and Texas Red Dextran without appreciable leakage into the soma compartment for over 15 hours. Compared to laminar-flow delivery of fluids with subcellular resolution, 74 this method does not have the complications associated with maintaining flow for long periods of time, but it does not allow for relocating the interface between the two fluids at will.…”

Section: Microfluidic Delivery Of Factors Tomentioning

confidence: 99%

“…An especially interesting application of this method is to stimulate only subcellular domains of single cells with multiple parallel laminar fluid flows. 74,75 Here, the interface between adjacent liquid streams is positioned over a single living cell so that different regions of the cell are exposed to different streams, allowing for treatment of subcellular domains of the cell. Using this technique, they were able to label different subpopulations of mitochondria with different fluorescent markers, disrupt selected regions of the cytoskeleton with the membrane-permeant drug latrunculin, digest ECM proteins on limited areas of cell-substrate adhesions with trypsin (see Fig.…”

Section: Engineering Fluid Environmentsmentioning

confidence: 99%

See 1 more Smart Citation

Biology on a Chip: Microfabrication for Studying the Behavior of Cultured Cells

Tourovskaia

Folch

2003

Crit Rev Biomed Eng

173

140

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The ability to culture cells in vitro has revolutionized hypothesis testing in basic cell and molecular biology research and has become a standard methodology in drug screening and toxicology assays. However, the traditional cell culture methodology-consisting essentially of the immersion of a large population of cells in a homogeneous fluid medium-has become increasingly limiting, both from a fundamental point of view (cells in vivo are surrounded by complex spatiotemporal microenvironments) and from a practical perspective (scaling up the number of fluid handling steps and cell manipulations for high-throughput studies in vitro is prohibitively expensive). Micro fabrication technologies have enabled researchers to design, with micrometer control, the biochemical composition and topology of the substrate, the medium composition, as well as the type of neighboring cells surrounding the microenvironment of the cell. In addition, microtechnology is conceptually well suited for the development of fast, low-cost in vitro systems that allow for high-throughput culturing and analysis of cells under large numbers of conditions. Here we review a variety of applications of microfabrication in cell culture studies, with an emphasis on the biology of various cell types.

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Section: Microfluidic Delivery Of Factors Tomentioning

confidence: 99%

Section: Engineering Fluid Environmentsmentioning

confidence: 99%

Biology on a Chip: Microfabrication for Studying the Behavior of Cultured Cells

Tourovskaia

Folch

2003

Crit Rev Biomed Eng

173

140

View full text Add to dashboard Cite

show abstract

“…As a demonstration, Takayama et al 13,24 adhered a bovine capillary endothelial (BCE) cell in a microfluidic channel and flowed Trypsin/EDTA locally over it, observing the detachment of the treated area. The simple microfluidic device consisted of three inlets from which the flows converged into a rectangular capillary as parallel laminar streams.…”

Section: Exploiting Microfluidic Flow For Unique Opportunities In Expmentioning

confidence: 99%

Microfluidics-based systems biology

2006

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Systems biology seeks to develop a complete understanding of cellular mechanisms by studying the functions of intra-and inter-cellular molecular interactions that trigger and coordinate cellular events. However, the complexity of biological systems causes accurate and precise systems biology experimentation to be a difficult task. Most biological experimentation focuses on highly detailed investigation of a single signaling mechanism, which lacks the throughput necessary to reconstruct the entirety of the biological system, while high-throughput testing often lacks the fidelity and detail necessary to fully comprehend the mechanisms of signal propagation. Systems biology experimentation, however, can benefit greatly from the progress in the development of microfluidic devices. Microfluidics provides the opportunity to study cells effectively on both a single-and multi-cellular level with high-resolution and localized application of experimental conditions with biomimetic physiological conditions. Additionally, the ability to massively array devices on a chip opens the door for high-throughput, high fidelity experimentation to aid in accurate and precise unraveling of the intertwined signaling systems that compose the inner workings of the cell.

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“…6). 100,101 This technique utilizes micrometer-sized streams of fluid flowing over spread mammalian cells. Due to the low velocity of the fluid flow and the small dimensions of the channel, low Reynolds number flow is established and the separated streams intersect in the main channel with minimal mixing.…”

Section: Nano-and Microtechnology To Address the Cytoskeletonmentioning

confidence: 99%

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

LeDuc

Bellin

2006

Ann Biomed Eng

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Abstract-Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano-and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.

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Subcellular positioning of small molecules

Cited by 512 publications

References 11 publications

Biology on a Chip: Microfabrication for Studying the Behavior of Cultured Cells

Biology on a Chip: Microfabrication for Studying the Behavior of Cultured Cells

Microfluidics-based systems biology

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

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