Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics

Kuo, Cheng-Tzu; Chiang, Chi‐Ling; Chang, Chia Hui; Liu, Hao-Kai; Huang, Guan-Syuan; Huang, Ruby Yun-Ju; Lee, Hsinyu; Huang, Chiun‐Sheng; Wo, Andrew M.

doi:10.1016/j.biomaterials.2013.11.008

Cited by 61 publications

(35 citation statements)

References 41 publications

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“…5,12 Furthermore, other research group had revealed that the stimulated intracellular calcium concentration is positively dependent on the corresponding molecule concentration, 13 which is consistent with our ondevice P-control (i.e., binding signal delivery) experiments ( Figure S3). 9 However, it is somewhat not consistent in micro/nano-scaled applications.…”

Section: B Demonstration Of Bindingless Signal Delivery In Et Modelsupporting

confidence: 88%

Experimental demonstration of bindingless signal delivery in human cells via microfluidics

Kuo

Chuang

et al. 2014

Journal of Applied Physics

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The cellular signal transduction is commonly believed to rely on the direct “contact” or “binding” of the participating molecule reaction that depends positively on the corresponding molecule concentrations. In living systems, however, it is somewhat difficult to precisely match the corresponding rapid “binding,” depending on the probability of molecular collision, existing in the cellular receptor-ligand interactions. Thus, a question arises that if there is another mechanism (i.e., bindingless) that could promote this signal communication. According to this hypothesis, we report a cellular model based on the examination of intracellular calcium concentration to explore whether the unidentified signal delivery in cells exists, via a microfluidic device. This device was designed to isolate the cells from directly contacting with the corresponding ligands/molecules by the particular polydimethylsiloxane (PDMS) membranes with different thicknesses. Results show a significant increment of calcium mobilization in human prostate cancer PC-3 cells by the stimulation of endothelin-1, even up to a separated distance of 95 μm. In addition, these stimulated signals exhibited a bump-shaped characteristics depending on the membrane thickness. When the PDMS membrane is capped by SiO2, a particular trait that resembles the ballistic signal conduction was observed. A theoretical model was developed to describe the signal transport process across the PDMS membrane. Taken together, these results indicate that the unidentified signal (ligand structural information) delivery could occur in cells and be examined by the proposed approach, exhibiting a bindingless communication manner. Moreover, this approach and our finding may offer new opportunities to establish a robust and cost-effective platform for the study of cellular biology and new drug development.

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Section: B Demonstration Of Bindingless Signal Delivery In Et Modelsupporting

confidence: 88%

Experimental demonstration of bindingless signal delivery in human cells via microfluidics

Kuo

Chuang

et al. 2014

Journal of Applied Physics

Self Cite

View full text Add to dashboard Cite

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“…Biomimetic microfluidic systems have been developed for spheroid formation 103,104 , intravasation 105 , extravasation 106 and angiogenesis 107,108 . For example, to investigate mechanisms by which the endothelial barrier is compromised in cancer cell invasion, researchers created a tumour-to-vascular interface using a multichannel microfluidic device.…”

Section: Tailored Contextsmentioning

confidence: 99%

Microfluidics: reframing biological enquiry

Duncombe

Tentori

Herr

2015

Nat Rev Mol Cell Biol

279

202

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The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools — in conjunction with advanced imaging, bioinformatics and molecular biology approaches — will transform biology into a precision science.

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“…Using such devices, Kuo et al [164,165] found decreased EpCAM expression in migratory cells, suggesting that the cells underwent the EMT and gained invasive properties.…”

Section: Metastatic Niche: Modelling Tumour -Stroma Interaction and Mmentioning

confidence: 99%

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

Tsai

Trubelja

Shen

et al. 2017

J. R. Soc. Interface.

172

133

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Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening. In particular, tumour-on-a-chip microdevices allow well-controlled microscopic studies of the interaction among tumour cells, immune cells and cells in the TME, of which simple tissue cultures and animal models are not amenable to do. The challenges in developing the next-generation tumour-on-a-chip technology are also discussed.

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Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics

Cited by 61 publications

References 41 publications

Experimental demonstration of bindingless signal delivery in human cells via microfluidics

Experimental demonstration of bindingless signal delivery in human cells via microfluidics

Microfluidics: reframing biological enquiry

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

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