Prestress and adhesion site dynamics control cell sensitivity to extracellular stiffness
S. Féréol, R. Fodil, V.M. Laurent, M. Balland, B. Louis, G. Pelle, S. Hénon, E. Planus, and D. Isabey
Biophysical Journal 96, 2009-2022 (2009) [Accès à la revue]
Cet article apporte des arguments théoriques et expérimentaux montrant comment et pourquoi l'environnement mécanique extracellulaire (par exemple la rigidité du substrat) et l'activité contractile intracellulaire (tension interne notamment générée par les moteurs acto-myosine) contrôlent l'activation des sites d'adhésion cellulaire. En résumé, l'énergie mécanique extra et intracellulaire contrôle, en la ralentissant, l'activation chimique des sites dynamiques d'adhésion cellulaire, les rendant sensibles aux propriétés mécaniques de l'environnement.
Abstract: This study aims at improving the understanding of mechanisms responsible for cell sensitivity to extracellular environment. We explain how substrate mechanical properties can modulate the force-regulation of cell sensitive elements primarily adhesion sites. We present a theoretical and experimental comparison between two radically different approaches of the force-regulation of adhesion sites which depends on their either stationary or dynamic behavior. The most classical stationary model fails to predict cell sensitivity to substrate stiffness while the dynamic model predicts extracellular stiffness dependence. This is due to a time-dependent reaction force in response to actomyosin traction force exerted on cell sensitive elements. We purposely used two cellular models, i.e., alveolar epithelial cells (AECs) and alveolar macrophages (AMs) exhibiting respectively stationary and dynamic adhesion sites, and compared their sensitivity to theoretical predictions. Mechanical and structural results show that AECs exhibit significant prestress supported by evident stress fibers and lacks sensitivity to substrate stiffness. On the other hand, AMs exhibit low prestress and exhibit sensitivity to substrate stiffness. Altogether, theory and experiments consistently show that adhesion site dynamics and cytoskeleton prestress control cell sensitivity to ECE with an optimal sensitivity expected in the intermediate range.
Thème : Thème 2007-2010 : Mécanique cellulaire
Equipe : Biomécanique Cellulaire et Respiratoire (IMRB)