Microfluidics technology for research on dynamics of paracrine signaling

Cells like other organisms have their own way of communication. The communication between cells is called intercellular signaling. Intercellular signaling normally occurs via small soluble or volatile chemicals called ligands. The ligands interact and bind with specific proteins in the target cell called receptors. There are various types of intercellular signaling based on the distance the ligand travels. Autocrine signaling occurs when a cell targets itself while endocrine signaling happens when the target cell is distant.  Paracrine signaling aims at targeting nearby cells and is of particular interest in tissue repair. However, temporal intercellular signaling at the paracrine level is challenging to analyze since it requires a microsystem that allows the culturing of multiple cell types as well as controlling the microenvironments individually. This is very difficult using traditional cell culturing methods and requires advanced cell culturing using microfluidics.

Recently, a reconfigurable microfluidic device for spatiotemporal dynamics of paracrine signaling was reported in Nature Biomedical Engineering journal by a group of researchers from the University of Wisconsin-Madison and University of Washington, Seattle. They employed microfluidics fabrication techniques to develop a stackable microfluidic chip for culturing multiple cell types (called Stacks). They leveraged open and suspended microfluidic concepts to enable a 2D and 3D layer of cell culture to be prepared individually. Their device consisted of multiple layers that could be manipulated individually up until to the point where they were ready to be stacked. The design of the device allows any desirable configuration for stacking the layers. The layers could be stacked and unstacked at any time over the course of the experiment. This facilitates individual imaging of each layer during the experiment as well as reconfiguring the layers for analyzing sequential paracrine-signaling events.

“Our proof-of-concept experiments exemplify how Stacks can efficiently model multicellular interactions and highlight the importance of spatiotemporal specificity in intercellular signaling.”, the authors explained. 

A comparison of the design with conventional Transwell assays showed the superiority of the reported device. As opposed to the Transwell, Stacks allowed flow channels through each layer and individual access to each layer. The average cost was estimated to be around $20 USD which is 15 times cheaper than th3 $300 for Transwell assays.

Link to the original article: Reconfigurable open microfluidics for studying the spatiotemporal dynamics of paracrine signalling