DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

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completely understood, they seem to transduce mechanical stimuli by modulating Wnt
and Sonic Hedgehog singaling or/ and gating polycystin-based ion channels
(Wallingford, 2010; Wallingford and Mitchell, 2011; Bisgrove and Yost, 2006; Berbari et
al., 2009).
I.2.2 - Extracellular matrix and integrin-based mechanotransduction
mechanisms
The extracellular matrix (ECM) mediates changes in cell shape according to its
mechanical properties and most adherent cells have a very their own shape but nonadherent
cell types are usually rounded and change shape when they attach to
surrounding tissue (Discher et al., 2009), suggesting that adherent cells can sense and
respond to mechanical signals from the ECM. The regulated interplay of intracellular
contractile forces and extracellular attachment might determine cellular shapes (Bauer
et al., 2009). Focal adhesions and other membrane sensors (e.g. tight junctions and
primary cilia) alter their structure and function as a result of changes in mechanical
stress when cells are attached to substrates of different stiffness (Chen et al., 2008).
Changes in stiffness can cause a change in cell shape and it is observed that
cells retain a more rounded morphology on soft substrates and take on a more
flattened shape on stiff substrates (normally associated with cells cultured on hard
tissue culture polystyrene) (Chen et al., 2008).
I.2.2.1 - Mechanisms of Rigidity Sensing
Substrate rigidity, besides changing cell shape can also influence a number of
cellular processes including retraction forces, cell adhesion, actin flow, gene
expression, and cell lineage (Bard and Hay, 1975; Choquet et al., 1997; Engler et al.,
2006; Lo et al., 2000; Pelham and Wang, 1997; Peyton and Putnam, 2005). The nature
of the matrix and the cell-type specific components involved in the responses will
define the rigidity responses. However, in a basic way, integrin-mediated rigidity
sensing can be taken as the decision to couple and reinforce the link between an