Magnetic nanoparticle–mediated massively parallel mechanical modulation of single-cell behavior

Tseng, Peter; Judy, Jack W.; Carlo, Dino Di

doi:10.1038/nmeth.2210

Cited by 181 publications

(171 citation statements)

References 44 publications

(46 reference statements)

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“…Several approaches have been designed for this purpose, e.g., inkjet cell printing (3)(4)(5)(6), surface engineering (7)(8)(9)(10)(11)(12)(13)(14)(15), and physical constraints (16)(17)(18)(19)(20)(21)(22)(23). However, finding a method that completely satisfies the above requirements remains a challenge.…”

mentioning

confidence: 99%

Block-Cell-Printing for live single-cell printing

Zhang¹,

Chou

Xia

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

129

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A unique live-cell printing technique, termed "Block-Cell-Printing" (BloC-Printing), allows for convenient, precise, multiplexed, and high-throughput printing of functional single-cell arrays. Adapted from woodblock printing techniques, the approach employs microfluidic arrays of hook-shaped traps to hold cells at designated positions and directly transfer the anchored cells onto various substrates. BloC-Printing has a minimum turnaround time of 0.5 h, a maximum resolution of 5 μm, close to 100% cell viability, the ability to handle multiple cell types, and efficiently construct protrusion-connected single-cell arrays. The approach enables the large-scale formation of heterotypic cell pairs with controlled morphology and allows for material transport through gap junction intercellular communication. When six types of breast cancer cells are allowed to extend membrane protrusions in the BloC-Printing device for 3 h, multiple biophysical characteristics of cells-including the protrusion percentage, extension rate, and cell length-are easily quantified and found to correlate well with their migration levels. In light of this discovery, BloC-Printing may serve as a rapid and high-throughput cell protrusion characterization tool to measure the invasion and migration capability of cancer cells. Furthermore, primary neurons are also compatible with BloC-Printing.cell array | cell communication | protrusion profiling | neuron patterning C urrent high-throughput screening of cell function and heterogeneity and in vitro cell-cell communication studies requires routine generation of large-scale single-cell arrays with high precision and efficiency, single-cell resolution, multiple cell types, and maintenance of cell viability and function (1, 2). Several approaches have been designed for this purpose, e.g., inkjet cell printing (3-6), surface engineering (7-15), and physical constraints (16-23). However, finding a method that completely satisfies the above requirements remains a challenge. Potentially useful and convenient tools may be available by adapting traditional printing tools to cell printing. In particular, woodblock printing is an efficient and convenient technology that revolutionized the printing world more than 1,800 y ago and was extended to microcontact molecular printing ∼20 y ago (24). However, application of the block-printing concept to cells has never been achieved. The main challenges are (i) inking cells to their molds with precision and maintaining viability, (ii) evenly and gently applying and transferring the cells to a substrate and successfully lifting off the mold without detaching the cells, and (iii) maintaining cell functions after printing.We report here the development and testing of a technology called "Block-Cell-Printing" (BloC-Printing), which involves directly inking cells to a predesigned mold and then transferring the cells to a substrate. We overcome the challenges described above by flow patterning, instead of pressing, the ink objects, as in woodblock or microcontact printing. By ...

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mentioning

confidence: 99%

Block-Cell-Printing for live single-cell printing

Zhang¹,

Chou

Xia

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

129

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“…Micro-devices patterned with magnetic elements have been fabricated to establish steep magnetic gradients to enhance the magnetization of MNPs and resulting forces on neurons. 53 It has been shown that internalized MNPs can influence the protein tau distribution which affects the polarization of neurites for axon formation. 54 Calcium is an important second messenger that is implicated in various signaling pathways that regulate gene expression.…”

Section: Nano-technology Toolsmentioning

confidence: 99%

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

Tay

2018

Springer Theses

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Neural stimulation techniques for eliciting calcium influx can elucidate the physiological roles of specific neural populations. To overcome some of the limitations of existing techniques such as poor specificity and noxious effects of heat, I developed a technology for non-invasive control of neural activities using magnetic forces and magnetic nanoparticles (MNPs) which offer deep tissue penetration and controllable dosage. Extensive investigations with different neurotoxins and experimental conditions support that the mechanism of magnetic stimulation that involves membrane-bound MNPs transducing magnetic forces into mechanical stretching of the cell membrane to enhance the opening probability of mechano-sensitive N-type calcium ion channels to induce calcium influx.Making use of the ability of neural networks to actively regulate their ratio of excitatory to inhibitory ion channel/receptor, I also performed chronic magnetic stimulation on fragile X iii syndrome (FXS) model neural networks. We found that chronic magnetic stimulation reduced the density of N-type calcium ion channels whose expression is increased in FXS. This technique demonstrates the potential of using bio-magnetic/mechanical forces to modulate expressions of mechano-sensitive ion channels where they are over-expressed in diseases such as abnormal nociception.Nonetheless, there are still a few areas where the technique can be improved. Firstly, it is the use of MNPs with more uniform properties to have greater control on magnetic stimulations.Secondly, the technique needs to be useful for in vivo studies. Therefore, I started researching on magnetotactic bacteria (MTB) which produce biological MNPs with superior properties such as uniform sizes and highly homogenous magnetic properties with the goal of harvesting MNPs from them.MTB, however, grow extremely slowly and the number of MNPs produced/bacterium is low. One way to overcome this problem is to evolve MTB over-producers of MNPs but this strategy is constrained by the absence of a selection platform that is quantitative and offer high throughput. To overcome this problem, I combined random chemical mutagenesis and selection using a magnetic ratcheting platform to generate and isolate MTB over-producers that produce twice as many MNPs/bacterium after 5 rounds of mutation/selection. I next designed a magnetic microfluidic device and demonstrate as a proof of concept, that it can be coupled to a bioreactor for high throughput microfluidic selection of MTB over-producers.iv

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“…smallest diameter of the concentrated circle) and 10-20 μm effective length. Note that relocalization of the proteins was induced by force-induced active transport ( Etoc et al, 2013 ;Hoffmann et al, 2013 ;Mannix et al, 2008 ;Tseng et al, 2012 ), rather than by passive diffusion followed by trapping of proteins as in optogenetic methods ( Levskaya et al, 2009 ). This property of MPNs is advantageous for directing the reorganization of confined or slowly diffusing membrane proteins such as Notch and E-cadherin receptors ( Farlow et al, 2013 ).…”

Section: Nanoprobe-mediated Spatial Reorganization and Force-inducedmentioning

confidence: 99%

“…Microprobe-based force microscopy tools can deliver a specific force to purified biomolecules ( Dufrêne et al, 2011 ;Neuman and Nagy, 2008 ), but, due to the large size and multivalent character of microprobes, these tools are not ideal for spatial control of individual membrane proteins in live cells due to their propensity to cluster upon binding (Details in Result sections). Magnetic nanoparticles were previously used for controlling the subcellular distribution of proteins ( Bharde et al, 2013 ;Cho et al, 2012 ;Etoc et al, 2013 ;Hoffmann et al, 2013 ;Mannix et al, 2008 ;Tseng et al, 2012 ), but have not been used for mechanical loading of single biomolecules with controlled force. Therefore, new experimental tools are needed to probe the spatial, temporal, chemical, and mechanical regulation of mechanosensitive membrane proteins in a single and integrated platform.…”

Section: Introductionmentioning

confidence: 99%

A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time

Seo¹,

Southard²,

Kim³

et al. 2017

Cell

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SUMMARYTools capable of imaging and perturbing mechanical signaling pathways with fine spatiotemporal resolution have been elusive despite their importance in diverse cellular processes. The challenge in developing a mechanogenetic toolkit (i.e. selective and quantitative activation of genetically encoded mechanoreceptors) stems from the fact that many mechanically-activated processes are localized in space and time, yet additionally require mechanical loading to become activated. To Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access

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Magnetic nanoparticle–mediated massively parallel mechanical modulation of single-cell behavior

Cited by 181 publications

References 44 publications

Block-Cell-Printing for live single-cell printing

Block-Cell-Printing for live single-cell printing

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

A Mechanogenetic Toolkit for Interrogating Cell Signaling in Space and Time

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