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International Conference on Mathematical Biology and

Annual Meeting of The Society for Mathematical Biology,

July 27-30, 2009

University of British Columbia, Vancouver



Normand Marceau
Centre de recherche en cancerologie, Laval University
Title Keratin involvement in simple epithelial cell response to a mechanical stress or a migratory stimulus
Abstract The capacity of cells to sense and adapt to mechanical stress applied on extracellular matrix (ECM)-integrin-cytoskeleton connections at focal adhesions (FAs) is crucial for basic cell behaviors, like migration. In migratory cells, new linkages between ECM and integrins are formed at FAs, and used as sites for the application of actin cytoskeleton-generated force at the cell front. Conversely, upon ECM deformation cells experience a mechanical stress that is transmitted to actin microfilaments through cytoskeletal linkers that also bind integrins. In the work reported here we assessed the contribution of keratin 8/18 (K8/K18) intermediate filaments (IFs) in simple epithelial cells in their response to a mechanical stress or a migratory stimulus, using monolayer cultures of K8-knockdown H4-II-E-C3 (shK8b1) rat hepatoma cells and their K8/K18-containing counterparts (H4ev). The mechanical stress was generated with a laser tweezer-mediated force applied on a fibronectin-coated microbead attached to integrins, and the cell response was assessed by the bead displacement. Notably, de-polymerization of actin microfilaments and microtubules led to increased bead displacements relative to untreated H4ev cells, whereas the loss of the K8/K18 IF network yielded a decrease in bead displacement in shK8b1 cells. In a comparable way, using scratch wound and single-cell migration assays, shK8b1 cells were found to migrate less than H4ev cells upon seeding on fibronectin. Finally, the K8/K18 loss was found to perturb the plectin/ receptor of activated C kinase 1(RACK1)/protein kinase C involvement in the integrin-mediated response to mechanical stress or migratory stimulus, in support of our model by which K8/K18 IFs, along with plectin and RACK1, constitute a versatile signaling platform in simple epithelial cells.
Work supported by CIHR and NSERC
(in collaboration with François Bordeleau1,2, Luc Galarneau1 and Yunlong Sheng2. 1Centre de recherche en cancérologie and 2Centre de recherche en optique, photonique et laser, Laval University, Quebec City, G1K 7P4, Canada.)
LocationWoodward 3