Pelling
Lab.net

The Pelling Lab is generally interested in understanding dynamic mechanical properties of cellular systems across nanometer and micrometer length scales. Utilizing a combination of cell biology, molecular biology, physical and computational approaches we are attempting to understand the fundamental genetic and architectural control mechanisms of mechanotransduction pathways in cells and artificial tissues. A combination of biophysical tools allow us to probe the force transduction and response pathways of single cells (adherent and non-adherent), multi-cellular aggregates and artificial tissues at local and global scales simultaneously controlling their mechanical, biochemical and physiological environments. Below you will find some representative publications and a general overview of the research taking place in the lab. Detailed and up to date information can be found on the Publications \\ page.

Understanding Force Transduction Through The Cyto-Architecture

Utilizing simultaneous atomic force microscopy (AFM) and high speed resonant scanning confocal microscopy we are visualizing the deformation pathways through multiple elements of the cyto-architecture. Force transduction is controlled by multiple elements of the cytoskeleton in pathways dependent on the cell type, the physiological conditions and the properties of the mechanical microenvironment.

The AFM tip (red) above a live cell expressing GFP-Actin (green)
Publications

• Hemsley, A.L., Hernandez, D., Pelling, A.E. & Veraitch, F.S. "Precisely delivered nano-mechanical forces induce blebbing in undifferentiated mouse embryonic stem cells." Cell Health and Cytoskeleton 3, 23 (2011)
• Pelling, A.E., Veraitch, F.S., Chu, C.P.K., Mason, C. & Horton, M.A. "Mechanical Dynamics of Single Cells During Early Apoptosis." Cell Motil Cytoskeleton 66, 409 (2009).
• Silberberg, Y.R., Pelling, A.E., Yakubov, G.E., Crum, W.R., Hawkes, D.J. & Horton, M.A. "Mitochondrial Displacements in Response to Nanomechanical Forces." J Mol Recognit. 21, 30 (2008).
• Silberberg, Y.R., Guolla, L. & Pelling, A.E. "Investigating Mammalian Cell Nanomechanics with Simultaneous Optical and Atomic Force Microscopy." Dufrene, Y.F. ed. Life at the Nanoscale: Atomic Force Microscopy of Live Cells. Singapore: Pan Stanford Publishing, In Press (2011).
• Pelling, A.E., Nicholls, B.M., Silberberg, Y.S. & Horton, M.A. "Approaches for Investigating Mechanobiologial Dynamics in Living Cells with Combined Fluorescence and Atomic Force Microscopies." In Méndez-Vilas, A. and Díaz, J. eds. Modern Research and Educational Topics on Microscopy. Badajoz: Formatex, pp.3-10 (2007).

Mechanics of Cell Monolayers

In-vivo, cells are found within complex three dimensional environments in which the extra-cellular matrix, (ECM) cell-cell contacts/junctions and the mechanical properties of the surrounding micro-environment all play critical roles in governing and modulating the mechancial responses of cells to external forces. We are currently studying the role the ECM plays in determing the mechancial properties of cell sheets and its role in maintaining sheet integrity during cell death. We are also studying how mechanical forces are tranduced through cell sheets and the structural response of cellular monolayers to highly controlled mechancial stimulation.

  


Actin (red) and nuclei (blue) an an MDCK cell monolayer.
Publications

• Wang, J. & Pelling, A.E. "Cell Sheet Integrity and Nanomechanical Breakdown During Programmed Cell Death." Med Biol Eng Comput 48, 1015 (2010).
  
• Hogan, C., Dupre-Crochet, S., Norman, M., Kajita, M., Zimmermann, C., Pelling, A.E., Piddini, E., Baena-Lopez, A., Vincent, J., Itoh, Y., Hosoya, H., Pichaud, F. & Fujita, Y. "Characterization of the Interface Between Normal and Transformed Epithelial Cells." Nat Cell Biol 11, 460 (2009)

Mechanical Microenvironments

The mechanical micro-environment (MME) is a critical factor in governing cellular responses to external forces and directing important physiological pathways such as apoptosis, differentiation and myogenesis. We have previously shown that the MME affects the mechancial breakdown of single cells during apoptosis by altering cytoskeletal remodelling possibly by modulating caspase activity. We are currently utilizing traction force microscopy (TFM) to study live cell mechanosensitivity in MME's which mimic working and resting tissues by examining cytoskeletal and focal adhesion remodelling during cellular traction force generation.














Publications

• Pelling, A.E., Veraitch, F.S., Chu, C.P.K., Mason, C. & Horton, M.A. "Mechanical Dynamics of Single Cells During Early Apoptosis." Cell Motil Cytoskeleton 66, 409 (2009).
• Al-Rekabi, Z., Harden, J.L. & Pelling, A.E. "Cellular Nanomechanics in Nanomedicine." In Bartul, Z. & Trenor, J. eds. Advances in Nanotechnology. Nova Science Publishers, pp.275-296 (2010).
• Silberberg, Y.R., Guolla, L. & Pelling, A.E. "Investigating Mammalian Cell Nanomechanics with Simultaneous Optical and Atomic Force Microscopy." Dufrene, Y.F. ed. Life at the Nanoscale: Atomic Force Microscopy of Live Cells. Singapore: Pan Stanford Publishing, In Press (2011).

Funding