Cell invasion in digital microfluidic microgel systems

Li, Bingyu B.; Scott, Elaine P.; Chamberlain, M. Dean; Duong, Bill; Zhang, Shuailong; Done, Susan J.; Wheeler, Aaron R.

doi:10.1126/sciadv.aba9589

Cited by 27 publications

(32 citation statements)

References 55 publications

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“…In vitro invasion assays typically involve 3D hydrogel lattices, such as Matrigel, through which cultured metastatic cancer cells will invade in response to chemo-attractants [7]. Recently, microfluidic systems have been integrated with collagen matrices to improve these in vitro investigations of cellular invasion [8]. While in vitro invasion models provide an efficient means to study the mechanical aspects of cellular invasion, they are currently unable to replicate the complex microenvironment in which cells must invade during animal development and disease.…”

Section: Introductionmentioning

confidence: 99%

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo

Smith

Xiao

et al. 2022

PLoS Genet

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Chromatin remodelers such as the SWI/SNF complex coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in genes encoding the structural subunits of chromatin, such as histone subunits, and chromatin regulating factors are associated with a variety of disease mechanisms including cancer metastasis, in which cancer co-opts cellular invasion programs functioning in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin agents and chromatin regulating factors that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and enhanced RNA interference (RNAi) vectors, we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Our data specifically implicate the SWI/SNF BAF assembly in the regulation of the G0 cell cycle arrest in the AC, whereas the SWI/SNF PBAF assembly promotes AC invasion via cell cycle-independent mechanisms, including attachment to the basement membrane (BM) and activation of the pro-invasive fos-1/FOS gene. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into how the SWI/SNF assemblies differentially contribute to cellular invasion and how SWI/SNF subunit-specific disruptions may contribute to tumorigeneses and cancer metastasis.

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Section: Introductionmentioning

confidence: 99%

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo

Smith

Xiao

et al. 2022

PLoS Genet

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“…In the last decades, digital microfluidics (DMF) have attracted widespread attention as a new lab-on-a-chip approach for programmable manipulating of droplets at the volume of nano-to-micro liters [1,2]. The droplets on the DMF chip can be actuated in parallel to mix, separate, and dispose, which can be used in wide applications such as chemical reactions, automatic detection, and cell culture [3][4][5]. DMF based on electrowetting on dielectric (EWOD) is promising to be used in portable applications such as deployable environmental monitoring and point-of-care testing (POCT) [6], since it drives the droplets only requiring configuration of the voltage applied on an electrode array, which has advantages including accurate volume control, small size, low reagent cost, and low power consumption [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…As various methods have been developed to fabricate DMF chips based on substrates such as silicon wafer, ITO glass, PCB board, and flexible polymers, the DMF technique is able to combine with a variety of analytical methods such as electrochemiluminescence [12], electrochemistry [13], and colorimetric sensing [14]. Currently, the EWOD-based DMF has been widely used in biosensing, environmental monitoring, and food safety, such as single-cell sequencing [2,15], cell invasion monitoring [5], detection of growth factors in embryo culture medium [9], bacterial classification [16], marine pollution monitoring [17], and detection of food nitrite [14].…”

Section: Introductionmentioning

confidence: 99%

Colorimetric Sensing with Gold Nanoparticles on Electrowetting-Based Digital Microfluidics

Luo

Ding

et al. 2021

Micromachines

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Digital microfluidic (DMF) has been a unique tool for manipulating micro-droplets with high flexibility and accuracy. To extend the application of DMF for automatic and in-site detection, it is promising to introduce colorimetric sensing based on gold nanoparticles (AuNPs), which have advantages including high sensitivity, label-free, biocompatibility, and easy surface modification. However, there is still a lack of studies for investigating the movement and stability of AuNPs for in-site detection on the electrowetting-based digital microfluidics. Herein, to demonstrate the ability of DMF for colorimetric sensing with AuNPs, we investigated the electrowetting property of the AuNPs droplets on the hydrophobic interface of the DMF chip and examined the stability of the AuNPs on DMF as well as the influence of evaporation to the colorimetric sensing. As a result, we found that the electrowetting of AuNPs fits to a modified Young–Lippmann equation, which suggests that a higher voltage is required to actuate AuNPs droplets compared with actuating water droplets. Moreover, the stability of AuNPs was maintained during the processing of electrowetting. We also proved that the evaporation of droplets has a limited influence on the detections that last several minutes. Finally, a model experiment for the detection of Hg2+ was carried out with similar results to the detections in bulk solution. The proposed method can be further extended to a wide range of AuNPs-based detection for label-free, automatic, and low-cost detection of small molecules, biomarkers, and metal ions.

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“…Asterisk indicates polarized F-actin driven protrusion extending ventrally. (H) Schematic summary of the how the SWI/SNF PBAF (orange – swsn-7 (7), swsn-9 (9), pbrm-1 (P)) and BAF ( swsn-8 (8), dpff-1 (D)) assemblies contribute to AC invasion.…”

Section: Resultsmentioning

confidence: 99%

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasionin vivo

Smith

Xiao

et al. 2021

Preprint

View full text Add to dashboard Cite

Chromatin remodeling complexes, such as the SWItching defective/Sucrose Non-Fermenting (SWI/SNF) ATP-dependent chromatin remodeling complex, coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in subunits of chromatin regulating factors are associated with a variety of diseases and cancer metastasis co-opts cellular invasion found in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin and chromatin regulating factors (CRFs) that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0/G1 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and RNA interference (RNAi), we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Finally, we implicate the SWI/SNF BAF assembly in the regulation of the cell cycle, whereas our data suggests that the SWI/SNF PBAF assembly promotes AC attachment to the basement membrane (BM) and promotes the activation of the invasive machinery. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into the contributions of SWI/SNF assembly and subunit-specific disruptions to tumorigenesis and cancer metastasis.

show abstract

Cell invasion in digital microfluidic microgel systems

Cited by 27 publications

References 55 publications

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo

Colorimetric Sensing with Gold Nanoparticles on Electrowetting-Based Digital Microfluidics

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasionin vivo

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