DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

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transduced to affect cellular signaling, gene expression and cell function, which are
crucial to developmental programming (Lee et al., 2006; Somogyi and Rorth, 2004;
Farge, 2003). (Ingber et al., 1986a; Ingber and Folkman, 1989b). It was shown that
changes in the balance of mechanical forces between integrins and cytoskeleton that
accompany cells spreading and drive cytoskeletal restructuring control downstream
mitogenic signaling cascades and thereby control the cellular response to other
external stimuli. So mechanical forces are equally important biological regulators as
growth factors and ECM are (Huang et al., 1998).
It has long been noted that the differentiation of stem cells into multiple
lineages is accompanied by dramatic changes in cell morphologies, and the
demonstration that mechanical cues influence lineage commitment of stem cells
(McBeath et al., 2004). So, inhibition of cell-generated forces was showed to alter
many basic cellular functions, such as proliferation, differentiation, tissue organization
and migration (Huang et al., 1998; McBeath et al., 2004; Sordella et al., 2003; Krieg et
al., 2008; Lo et al., 2004).
By modulating the stress that is generated by these cellular forces altering the
mechanical stiffness of the substrate it is possible to achieve a similar response to the
one caused by directly altering cellular contractility (Pelham and Wang, 1997; Paszek
and Weaver, 2004; Engler et al., 2006).
Stiffness is the extent to which a substrate resists deformation. Substrate
stiffness itself can alter numerous cellular functions including migration, proliferation
and differentiation (Li et al., 2007; Peyton and Putnam, 2005; Leach et al., 2007; Lo et
al., 2000).