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Cell sensitivity to substrate stiffness

Cell sensitivity to substrate stiffness

Submitted by Daniel Isabey on Wed, 2009-04-15 15:03.

In Féréol et al. (Biophys. J., 2009, 96: 2009-2022),
we propose a coupled theoretical and experimental study in order to understand the
mechanism of cell sensitivity to substrate stiffness. To do so, we first consider
that adhesion sites pass through different stages of development, e.g., Initial
Adhesion (IA), Focal Complex (FC), Focal Adhesions (FA), characterized by the
recruitment of an increasing number of constituent components resulting in molecular
reinforcement of the links between CSK and extracellular environment. One
assumption is that as adhesion sites gain in molecular complexity and strength
(without necessarily increasing their area), they lose their dynamic character
and become more stationary, providing an evolutionary cell signaling which contributes
to cell adaptation. First, Newton’s action-reaction principle which governs the
static force equilibrium at a given stationary adhesion site demonstrates that stationary
adhesion sites (FA) could not exhibit such a substrate stiffness sensitivity. Second,
considering that the proper of dynamic adhesion site is to move relatively to
actin filament bundle, it appears that mechanical relaxation of the
extracellular environment as well as intracellular tensional properties tend to
slow down dramatically the “instantaneous” biochemical process of
receptor-ligand binding. Such an approach enlightens that force regulation of dynamic
adhesion site depends on mechanical properties of substrate and intracellular
properties which together act as a loading rate at the onset of a time-dependent
maturation in response to acto-myosin traction force. Early experiments with
optical tweezers used as a calibrated spring have already show that nascent (also
dynamic) adhesion sites match the force they exert on substrates of different stiffness
(Choquet et al. 1999 Cell 88: 39-48). Thus, different cells would produce
different cell responses that adapt to the wide variety of extracellular
mechanical environments and intracellular tensional conditions. We used two
cellular models, i.e., alveolar epithelial cells (AECs) and alveolar macrophages
(AMs), exhibiting markedly different mechanical behaviors (Féréol et al.,
Respir. Physiol. Neurobiol. 2008, 163: 3-16) and adhesion sites respectively in
stationary state (FA) and in dynamic state (podosome type adhesion system: PTA).
The cell sensitivity to substrate stiffness of these two cellular models appears
in good agreement with theoretical predictions.

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