Spatial gradients in intracellular signal transduction

9 March 2007

Jason Haugh
Department of Chemical and Biomolecular Engineering
N C State University


An ongoing challenge in mammalian cell biology is to bridge the gaps in our understanding of processes at the molecular, cellular, and tissue levels. Central to the hierarchy of biological complexity is the field of signal transduction, which deals with the biochemical mechanisms and pathways by which cells respond to external stimuli. Our group characterizes signal transduction networks through analysis of their kinetics and spatial patterns in cells.

Whether treated explicitly or implicitly, concentration gradients are ubiquitous in mass transfer processes and are often thought of as the "driving forces" for molecular diffusion (a source of confusion for many). This talk is focused on the relevance, modeling, and measurement of spatial concentration gradients in cell signaling.

I will first motivate the talk with the concept that significant molecular gradients are present and important in biology at a variety of length scales. Next, I will review in broad terms some of our recently published work, building up from diffusion-controlled signal transduction reactions and interactions in membranes (1) to the spatial distribution of phosphoinositide 3-kinase signaling in fibroblasts responding to platelet-derived growth factor gradients (2-5) and the chemotactic invasion of fibroblast populations during dermal wound healing (6). Finally, I will describe the analysis of a general membrane-binding/activation model that, when coupled with intracellular diffusion, allows for control of membrane-bound signaling proteins (e.g., Rho-family GTPases) by local cell morphology. Such a mechanism could play a prominent role in cell polarization and persistent cell migration.


  1. M I Monine, J M Haugh, "Reactions on cell membranes: comparison of continuum theory and Brownian dynamics simulations", J Chem Phys 123:074908 2005. PubMed
  2. I C Schneider, J M Haugh, "Spatial analysis of 3' phosphoinositide signaling in living fibroblasts, II: Parameter estimates for individual cells from experiments", Biophys J 86:599-608 2004. PubMed
  3. I C Schneider, E M Parrish, J M Haugh, "Spatial analysis of 3' phosphoinositide signaling in living fibroblasts, III: influence of cell morphology and morphological polarity", Biophys J 89:1420-1430 2005. PubMed
  4. I C Schneider, J M Haugh, "Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts", J Cell Biol 171:883-892 2005. PubMed
  5. J M Haugh, I C Schneider, "Effectiveness factor for spatial gradient sensing in living cells", Chem Eng Sci 61:5603-5611 2006.
  6. J M Haugh, "Deterministic model of dermal wound invasion incorporating receptor-mediated signal transduction and spatial gradient sensing", Biophys J 90:2297-2308 2006. PubMed

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