Microfluidic control of axonal guidance

Gu, Ling; Black, Bryan; Ordonez, Simon; Mondal, Angana; Jain, Ankur; Mohanty, Samarendra

doi:10.1038/srep06457

Cited by 20 publications

(8 citation statements)

References 20 publications

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Section: Hydrodynamic Effects On Cells On Standard Open Substratesmentioning

confidence: 99%

“…For example, open-space hydrodynamic devices have also been used to exert mechanical (shear) forces on selected cells in an open and immersed environment. Gu et al 216 assessed the impact of fluid flow on axonal migration, producing turning angles of up to 90° by applying flows. Microfluidic flow simulations indicated that an axon may experience significant bending forces due to cross-flow, which are likely to contribute to the observed axonal bending.…”

Section: Hydrodynamic Effects On Cells On Standard Open Substratesmentioning

confidence: 99%

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Hydrodynamics in Cell Studies

et al. 2018

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Hydrodynamic phenomena are ubiquitous in living organisms and can be used to manipulate cells or emulate physiological microenvironments experienced in vivo. Hydrodynamic effects influence multiple cellular properties and processes, including cell morphology, intracellular processes, cell–cell signaling cascades and reaction kinetics, and play an important role at the single-cell, multicellular, and organ level. Selected hydrodynamic effects can also be leveraged to control mechanical stresses, analyte transport, as well as local temperature within cellular microenvironments. With a better understanding of fluid mechanics at the micrometer-length scale and the advent of microfluidic technologies, a new generation of experimental tools that provide control over cellular microenvironments and emulate physiological conditions with exquisite accuracy is now emerging. Accordingly, we believe that it is timely to assess the concepts underlying hydrodynamic control of cellular microenvironments and their applications and provide some perspective on the future of such tools in in vitro cell-culture models. Generally, we describe the interplay between living cells, hydrodynamic stressors, and fluid flow-induced effects imposed on the cells. This interplay results in a broad range of chemical, biological, and physical phenomena in and around cells. More specifically, we describe and formulate the underlying physics of hydrodynamic phenomena affecting both adhered and suspended cells. Moreover, we provide an overview of representative studies that leverage hydrodynamic effects in the context of single-cell studies within microfluidic systems.

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Section: Hydrodynamic Effects On Cells On Standard Open Substratesmentioning

confidence: 99%

Section: Hydrodynamic Effects On Cells On Standard Open Substratesmentioning

confidence: 99%

Hydrodynamics in Cell Studies

et al. 2018

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“…Physical cues are in general electrical 2 and optical 3 ) in nature or any combination thereof. Focused laser beam has enabled modulation and generation of several chemical 4 5 and physical (force 3 6 and fluid flow 7 8 9 ) cues to influence axonal guidance. In general, the light-based methods for axonal guidance can be divided into two categories, indirect and direct.…”

mentioning

confidence: 99%

Spatial temperature gradients guide axonal outgrowth

Black¹,

Vishwakarma²,

Dhakal³

et al. 2016

Sci Rep

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Formation of neural networks during development and regeneration after injury depends on accuracy of axonal pathfinding, which is primarily believed to be influenced by chemical cues. Recently, there is growing evidence that physical cues can play crucial role in axonal guidance. However, detailed mechanism involved in such guidance cues is lacking. By using weakly-focused near-infrared continuous wave (CW) laser microbeam in the path of an advancing axon, we discovered that the beam acts as a repulsive guidance cue. Here, we report that this highly-effective at-a-distance guidance is the result of a temperature field produced by the near-infrared laser light absorption. Since light absorption by extracellular medium increases when the laser wavelength was red shifted, the threshold laser power for reliable guidance was significantly lower in the near-infrared as compared to the visible spectrum. The spatial temperature gradient caused by the near-infrared laser beam at-a-distance was found to activate temperature-sensitive membrane receptors, resulting in an influx of calcium. The repulsive guidance effect was significantly reduced when extracellular calcium was depleted or in the presence of TRPV1-antagonist. Further, direct heating using micro-heater confirmed that the axonal guidance is caused by shallow temperature-gradient, eliminating the role of any non-photothermal effects.

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“…Second, it combines both geometrical and AC field growth constraints to control the connections between the nodes, allowing constraint-free positioning of nodes relatively to each other. Compared to existing neurite guidance techniques, either by controlling adhesive cues 33 34 35 or using microfluidic grooves 36 or both 37 or other techniques 38 39 , our method allows a dynamic multiplexed manipulation of neurites within the same groove, which enables the precise relative positioning of several neurites at the same time. Using our technique, in-vitro neural networks would not be limited by their structural connectivity between nodes, allowing the creation of complex networks with more than three nodes.…”

Section: Resultsmentioning

confidence: 99%

Microfluidic neurite guidance to study structure-function relationships in topologically-complex population-based neural networks

Honegger

Thielen

Feizi

et al. 2016

Sci Rep

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The central nervous system is a dense, layered, 3D interconnected network of populations of neurons, and thus recapitulating that complexity for in vitro CNS models requires methods that can create defined topologically-complex neuronal networks. Several three-dimensional patterning approaches have been developed but none have demonstrated the ability to control the connections between populations of neurons. Here we report a method using AC electrokinetic forces that can guide, accelerate, slow down and push up neurites in un-modified collagen scaffolds. We present a means to create in vitro neural networks of arbitrary complexity by using such forces to create 3D intersections of primary neuronal populations that are plated in a 2D plane. We report for the first time in vitro basic brain motifs that have been previously observed in vivo and show that their functional network is highly decorrelated to their structure. This platform can provide building blocks to reproduce in vitro the complexity of neural circuits and provide a minimalistic environment to study the structure-function relationship of the brain circuitry.

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Microfluidic control of axonal guidance

Cited by 20 publications

References 20 publications

Hydrodynamics in Cell Studies

Hydrodynamics in Cell Studies

Spatial temperature gradients guide axonal outgrowth

Microfluidic neurite guidance to study structure-function relationships in topologically-complex population-based neural networks

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