title: New insights into mammalian signaling pathways using microfluidic pulsatile inputs and mathematical modeling.
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.
authors.affiliation: Biointerface Institute, North Campus Research Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA. takayama@umich.edu and Biophysics Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: M
authors.identifier: 0000-0002-2268-2335
authors.initials: M
authors.lastname: Sumit
authors.affiliation: Biointerface Institute, North Campus Research Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA. takayama@umich.edu and Michigan Centre for Integrative Research in Critical Care, North Campus Research, Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA and Department of Biomedical Engineering, University of Michigan, 1107 Carl A., Gerstacker Building, 2200, Bonisteel Blvd, Ann Arbor, MI 48109, USA and Macromolecular Science and Engineering Program, University of Michigan, 2300, Hayward Street, Ann Arbor, MI 48109, USA.
authors.forename: S
authors.initials: S
authors.lastname: Takayama
authors.affiliation: Department of Biomedical Engineering, University of Michigan, 1107 Carl A., Gerstacker Building, 2200, Bonisteel Blvd, Ann Arbor, MI 48109, USA and Department of Chemical Engineering, University of Michigan, Building 26, 2800 Plymouth Road, Ann Arbor, MI 48109, USA. linderma@umich.edu.
authors.forename: J J
authors.initials: JJ
authors.lastname: Linderman
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000502:physiology; D055641:Mathematical Concepts; D046210:Microfluidic Analytical Techniques; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D058615:Synthetic Biology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D007328:Insulin; D008024:Ligands; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta