Séminaire Exceptionnel
Mercredi 3 mai 2006 à 11h30
Tour 33, couloir 33-43, 2ème étage, salle de réunion

Dennis Discher
(Cell & Biophysics Lab, Upenn, Philadelphie)

Stem Cell & Nuclear Biophysics – Mechanics inside & outside the cell

Microenvironments and niches appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. While it is known that many pre-committed cell types ‘feel’ the softness of their matrix through contractile mechanisms that influence adhesions and cytoskeleton, the impact – if any – of matrix elasticity on naive stem cells is unknown and key to understanding microenvironments. Mesenchymal stem cells are shown to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, contrasting with the elasticity-insensitive commitment of differentiated cell types. We find soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Myosin-II inhibition blocks this elasticity-directed lineage specification. Elasticity-dependent expression profiles correlate Ras family activators with lineage-specific transcription factors and also highlight the adhesion-contractile balance across lineages. The results have significant implications for understanding physical effects of the in vivo microenvironment.