A universal microfluidic approach for integrated analysis of temporal homocellular and heterocellular signaling and migration dynamics

Microfluidics offers precise and dynamic control of microenvironments for the study of temporal cellular responses. However, recent research focusing solely on either homocellular (single-cell, population) or heterocellular response may yield insufficient output, which possibly leads to partial comp...

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Published in:Biosensors & bioelectronics 2022-09, Vol.211, p.114353-114353, Article 114353
Main Authors: Yang, Haowen, Sinha, Nidhi, Rand, Ulfert, Hauser, Hansjörg, Köster, Mario, de Greef, Tom F.A., Tel, Jurjen
Format: Article
Language:English
Subjects:
Cell migration
Cellular signaling
Dynamic stimulation
Microfluidics
Single-cell analysis
STAT dynamics
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Summary:Microfluidics offers precise and dynamic control of microenvironments for the study of temporal cellular responses. However, recent research focusing solely on either homocellular (single-cell, population) or heterocellular response may yield insufficient output, which possibly leads to partial comprehension about the underlying mechanisms of signaling events and corresponding cellular behaviors. Here, a universal microfluidic approach is developed for integrated analysis of temporal signaling and cell migration dynamics in multiple cellular contexts (single-cell, population and coculture). This approach allows to confine the desired number or mixture of specific cell sample types in a single device. Precise single cell seeding was achieved manually with bidirectional controllability. Coupled with time-lapse imaging, temporal cellular responses can be observed with single-cell resolution. Using NIH3T3 cells stably expressing signal transducer and activator of transcription 1/2 (STAT1/2) activity biosensors, temporal STAT1/2 activation and cell migration dynamics were explored in isolated single cells, populations and cocultures stimulated with temporal inputs, such as single-pulse and continuous signals of interferon γ (IFNγ) or lipopolysaccharide (LPS). We demonstrate distinct dynamic responses of fibroblasts in different cellular contexts. Our presented approach facilitates a multi-dimensional understanding of STAT signaling and corresponding migration behaviors. •A general microfluidic approach was developed to study temporal cellular responses in multiple cellular contexts in a single device.•Precise single cell seeding with bidirectional controllability was achieved manually.•The applicability of this approach was validated by exploring temporal STAT activation and cell migration dynamics.•Distinct STAT and migration dynamics were observed in stimulated fibroblasts between different cellular contexts.
ISSN:0956-5663
1873-4235
DOI:10.1016/j.bios.2022.114353