The push and pull of cell mechanics: defining a new mechanotransduction pathway regulating cellular interactions with the extracellular environment.

Angus Cameron (primary)
Barts Cancer Institute - Centre for Tumour Biology,
Queen Mary, University of London
Núria Gavara (secondary)
Institute of Bioengineering and School of Engineering & Materials Science
Queen Mary, University of London

Abstract

Fibroblasts are dynamic regulators of tissue development, structure and homeostasis. Inappropriate activation of fibroblasts centrally contributes to the pathophysiology of cancer and fibrotic disease. We have discovered a new Rho GTPase effector pathway, which provides a pivotal link between extracellular mechanical cues and cellular behaviour; the molecular mechanisms remain obscure. In this exciting project, we will combine state-of-the-art genetic models, coupled with biophysical techniques and advanced live-cell microscopy, to understand how this novel pathway regulates cellular mechanics. This interdisciplinary study provides a unique opportunity to explore how cells sense and respond to the physical world, with significant impact for disease.


References

  1. Quetier I, Marshall JT, Lachmann S, Casamassima A, Spencer-Dene B, Franco C, Worrall J, Rajeeve V, Howell M, Rosewell I, Cutillas P, Gerhardt H, Parker PJ, & Cameron AJ. Knockout of the PKN family of Rho effector kinases reveals a non-redundant role for PKN2 in developmental mesoderm expansion. Cell Reports. 2016 Jan 26;14(3):440-8
  2. Rosse C, Linch M, Kermorgant S, Cameron AJ, Boeckeler K, Parker PJ. PKC and the control of localized signal dynamics. Nature Rev Mol Cell Biol. 2010 Feb;11(2):103-12. Review.
  3. Gavara N & Chadwick RS. AFM –  Determination of the elastic moduli of thin samples and adherent cells using conical atomic force microscope tips. Nature nanotechnology. 2012 Nov; 7 (11), 733-736
  4. Gavara N & Chadwick RS. CSK quantification –  Relationship between cell stiffness and stress fiber amount, assessed by simultaneous atomic force microscopy and live-cell fluorescence imaging. Biomechanics and modelling in mechanobiology. 2016 Jun; 15 (3), 511-523
  5. Theocharidis G, Drymoussi Z, Kao AP, Barber AH, Lee DA, Braun KM, Connelly JT. Type VI collagen regulates dermal matrix assembly and fibroblast motility. Journal of Investigative Dermatology. 2016; 136(1): 74-83.

BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyPhysiology
Techniques & Approaches
BiochemistryBiophysicsChemistryEngineeringGeneticsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular Biology