DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

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Figure 2| Proteins related to the mechanosensory in Integrin-Mediated Rigidity
Sensing. The yellow boxes highlight the proteins wich bind directly to the depicted
domains.(A) FAK activity is regulated by mechanical forcebut does not bind integrins or
actin directly.(B) Stretching the p130Cas domain exposes its 15 tyrosine residues. (C)
Stretching of talin’s rod domain exposes vinculin binding sites (del Rioet al., 2009).(D)
Extension of filamin immunoglobulin repeats (labeled 1–24) has beenshown by AFM
(Furuike et al., 2001) and could regulate the binding of proteins.(E) a-actinin forms
antiparallel dimers; mechanical force could regulate thisdimerization or its association
with other proteins.Adapted fromMoore et al., 2010.
Figure 3| The Rigidity Sensing Cycle. In this rigidity sensing cycle scheme it is shown the
correlation between mechanosensory events as integrin/ECM catch bond formation,
stretching of talin (that recuitsvinculin and therefore reinforces the adhesion) and
stretching of FAK, leading to the disassembly and recycling of the adhesion, by the
activation of its kinase domain. Adapted from; Moore et al., 2010
Figure 4| Tissue Elasticity. Range of stiffness measured by the elastic modulus, E, of
some human solid tissues. Adapted fromEngler et al., 2006.
Figure 5| Images depicted on A) and B) quantify the morphological changes (mean ±
SEM) versus stiffness, E: shown are (A) cell branching per length ofprimary mouse
neurons, MSCs, and blebbistatin-treated MSCs and (B) spindle morphology of MSCs,
blebbistatin-treated MSCs, and mitomycin-C treated MSCs (open squares) compared
to C2C12 myoblasts (dashed line). Furthermore in C) MSCs change their morphology
developing increasingly branched, spindle, or polygonal shapes, respectively, when
cultured on matrices with the elastic modulus (E) respectively in the range typical of
brain (0.1–1 kPa), muscle (8– 17 kPa), or stiff crosslinked-collagen matrices (25–40
kPa). Blebbistatin blocks morphology changes due to stiffness (