Abstract

Diffusion of autocrine and paracrine signaling molecules allows cells to communicate in the absence of physical contact. This chemical-based, long-range communication serves crucial roles in tissue function, activation of the immune system, and other physiological functions. Despite its importance, few in vitro methods to study cell-cell signaling through paracrine factors are available today. Here, we report the design and validation of a microfluidic platform that enables (i) soluble molecule-cell and/or (ii) cell-cell paracrine signaling. In the microfluidic platform, multiple cell populations can be introduced into parallel channels. The channels are separated by arrays of posts allowing diffusion of paracrine molecules between cell populations. A computational analysis was performed to aid design of the microfluidic platform. Specifically, it revealed that channel spacing affects both spatial and temporal distribution of signaling molecules, while the initial concentration of the signaling molecule mainly affects the concentration of the signaling molecules excreted by the cells. To validate the microfluidic platform, a model system composed of the signaling molecule lipopolysaccharide, mouse macrophages, and engineered human embryonic kidney cells was introduced into the platform. Upon diffusion from the first channel to the second channel, lipopolysaccharide activates the macrophages which begin to produce TNF-α. The TNF-α diffuses from the second channel to the third channel to stimulate the kidney cells, which express green fluorescent protein (GFP) in response. By increasing the initial lipopolysaccharide concentration an increase in fluorescent response was recorded, demonstrating the ability to quantify intercellular communication between 3D cellular constructs using the microfluidic platform reported here. Overall, these studies provide a detailed analysis on how concentration of the initial signaling molecules, spatiotemporal dynamics, and inter-channel spacing affect intercellular communication.

Original languageEnglish (US)
Article number044104
JournalBiomicrofluidics
Volume8
Issue number4
DOIs
StatePublished - Jul 10 2014

Fingerprint

Paracrine Communication
Microfluidics
platforms
communication
Molecules
Communication
cells
molecules
Lipopolysaccharides
Macrophages
macrophages
kidneys
Cells
Cell signaling
Design aids
spacing
immune systems
Immune system
Autocrine Communication
temporal distribution

ASJC Scopus subject areas

  • Molecular Biology
  • Materials Science(all)
  • Genetics
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

Cite this

Microfluidic platform for the study of intercellular communication via soluble factor-cell and cell-cell paracrine signaling. / Byrne, Matthew B.; Trump, Lisa; Desai, Amit V.; Schook, Lawrence B; Gaskins, H Rex; Kenis, Paul J A.

In: Biomicrofluidics, Vol. 8, No. 4, 044104, 10.07.2014.

Research output: Contribution to journalArticle

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