New insights into mammalian signaling pathways using microfluidic pulsatile inputs and mathematical modeling

Integr Biol (Camb). 2017 Jan 23;9(1):6-21. doi: 10.1039/c6ib00178e.

Abstract

Temporally modulated input mimics physiology. This chemical communication strategy filters the biochemical noise through entrainment and phase-locking. Under laboratory conditions, it also expands the observability space for downstream responses. A combined approach involving microfluidic pulsatile stimulation and mathematical modeling has led to deciphering of hidden/unknown temporal motifs in several mammalian signaling pathways and has provided mechanistic insights, including how these motifs combine to form distinct band-pass filters and govern fate regulation under dynamic microenvironment. This approach can be utilized to understand signaling circuit architectures and to gain mechanistic insights for several other signaling systems. Potential applications include synthetic biology and biotechnology, in developing pharmaceutical interventions, and in developing lab-on-chip models.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cellular Microenvironment / physiology
  • Humans
  • Insulin / physiology
  • Ligands
  • MAP Kinase Signaling System / physiology
  • Mathematical Concepts
  • Microfluidic Analytical Techniques
  • Models, Biological*
  • NF-kappa B / physiology
  • Receptors, G-Protein-Coupled / physiology
  • Signal Transduction / physiology*
  • Synthetic Biology
  • Transforming Growth Factor beta / physiology

Substances

  • Insulin
  • Ligands
  • NF-kappa B
  • Receptors, G-Protein-Coupled
  • Transforming Growth Factor beta