RT Journal Article
SR Electronic
T1 Heterogeneity of single-cell mechanical responses to tumorigenic factors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 078154
DO 10.1101/078154
A1 Aldo Leal-Egaña
A1 Gaelle Letort
A1 Jean-Louis Martiel
A1 Andreas Christ
A1 Timothée Vignaud
A1 Caroline Roelants
A1 Odile Filhol
A1 Manuel Théry
YR 2016
UL http://biorxiv.org/content/early/2016/09/30/078154.abstract
AB Tumor development progresses through a complex path of biomechanical changes leading first to cell growth and contraction followed by cell de-adhesion, scattering and invasion. Tumorigenic factors may act specifically on one of these steps or have wider spectrum of actions, leading to a variety of effects and thus sometimes to apparent contradictory outcomes. Here we used micropatterned lines of collagen type-I/fibronectin on deformable surfaces to standardize cell behavior and to measure simultaneously cell size, speed of motion and the magnitude of the associated contractile forces at the level of a single cell. We analyzed and compared normal human breast cell line MCF10A in control conditions and in response to various tumorigenic factors. In all conditions, distinct populations of cells with a wide range of biomechanical properties were identified. Despite this heterogeneity, normal and transformed motile cells followed a common trend whereby size and contractile forces were negatively correlated with cell speed. Some tumorigenic factors, such as activation of ErbB2 or the loss of the beta subunit of casein kinase 2 (CK2), shifted the whole population towards a faster speed and lower contractility state. Treatment with transforming growth factor beta (TGF-β), induced some cells to adopt opposing behaviors such as extreme high contractility versus extreme low contractility. Thus, tumor transformation amplified the pre-existing population heterogeneity and led some cells to exhibit biomechanical properties that were more extreme than that observed with normal cells.