DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

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(FXs) and focal adhesions (FA), undergo through a maturating process controlled by actomyosin
contractility which can be modified by stiffness, shape or external application of force.(D, RIGHT):
molecular structure of FA. α/β: alpha and beta sub-units of integrins, Pax: paxillin, F: Force delivered by
actomyosin contraction. The clustering of integrins may induce RhoA signaling which leads to an
increase of myosin contractility and an unfolding of proteins. Adapted from Eyckmans et al., 2011.
I.2.1 - Mechanotransduction and mechanosensors
Generation of forces on the matrix can be sensed through integrins by 5 basic
mechanisms that have been suggested for mechano-sensing: catch bond formation,
channel opening, enzyme regulation, exposure of phosphorylation sites, or exposure of
binding sites. All could play significant roles in adhesion-related processes (Moore et
al., 2010).
Looking over mechanotransduction more closely, it is known that changes in
cell shape and cytoskeletal architecture are related with the integrins binding and
clustering against ECM ligands, anchoring the actin cytoskeleton to sites of adhesion.
The orientation of the integrin layer within the cell membrane is made with the
head domains connecting to the ECM and the cytoplasmic tails binding to focal
adhesion kinase (FAK) and paxillin. This cytoplasmatic layer is assembled with
complexes containing talin and vinculin, and an uppermost actin-regulatory sheet
consisting of zyxin, VASP and α-actinin that binds the cytoskeleton to the FA (Figure
1D) (Kanchanawong et al., 2010).
Since the cytoskeleton is linked to the nuclear envelope, forces experienced or
generated by the cell-ECM module (Figure 1) are transmitted and sensed throughout
as a coordinated system (Eyckmans et al., 2011). The actomyosin cytoskeleton works
as a connection between multiple parts of the cell membrane as well as the cell
membrane to the nucleus (Sims et al., 1992). These filaments anchor into clusters of
proteins (including focal adhesions, FAs) which link the ECM to the cytoskeleton
through transmembrane integrin receptors (Eyckmans et al., 2011). So if there is
application of a force to the cell-ECM unit, structural deformations and
rearrangements of the ECM will occur, the force is transmitted through the FA, and
almost every single aspect of the intracellular structure, like the position of
endoplasmic reticulum, mitochondria and the nucleus will get deformed (Figure