Design Concept of Topographical and Mechanical Properties of Synthetic Extracellular Matrix to Control Cell Functions and Fates Through Actin Cytoskeletal Modulation - Innovative Approaches to Cell Biomechanics - page 158

Cell Nucleus

Nuclear Membrane

Chromatin

Lamin s

Nesprin

MLC MLC YAP/TAZ

P

Myosin

ROCK

MLCK

Actin Cytoskeleton

Rho GDP Rho GTP

α -Actinin

Ak t

ERK

Zyxin

Focal Adhesion
Complex

PI3K Vinculin

Talin

GEF

MEK

Raf

Ras Paxillin

Src

FAK

Plasma Membrane

Integrins

Extracellular Matrix

Fig. 11.2 Major mechanical and mechanochemical link between the cytoplasm and extracellular
matrix (ECM) (Miyoshi and Adachi 2014). The link contributes for cells to sense, integrate, trans-
duce, and respond to mechanical cues provided by ECM (Sun and Fu 2013 ; Wang et al. 2009 ;
Provenzano and Keely 2011 ; MacQueen et al. 2013 ; Sun et al. 2012 ). The actin cytoskeleton trans-
mits mechanical perturbations caused by ECM topography and stiffness, both directly ( right-hand
part ) and indirectly ( left-hand part ) to the cell nucleus (Adapted with permission from Mary Ann
Liebert, Inc. publishers: [Tissue Engineering Part B], copyright (2014))

Direct Mechanical Link

A typical direct mechanical link between the cytoplasm and ECM is shown in the
right-hand part of Fig. 11.2 . The cell adheres to ECM through molecular complexes
at multiple parts of the cell membrane at the interface of the cell and its extracellular
environment. Integrins bind to adhesive ligands of ECM via their extracellular
domains, and on the intracellular side, their cytoplasmic domains form a protein
complex that is linked to the actin fi lament (Berrier and Yamada 2007 ; Wehrle-
Haller 2012 ). The profi le of the proteins assembled at the protein complex, such as
paxillin, focal adhesion kinase (FAK), talin, vinculin, and zyxin, determines proper-
ties of the adhesive complex as a molecular clutch that links the actin cytoskeleton
to ECM-bound integrins, whereby forces of different magnitude are transmitted
from the cell to ECM and vice versa (Dumbauld et al. 2013 ; Roca-Cusachs et al.
2013 ; Boettiger 2012 ). The protein profi le, and the proteins' association and disso-
ciation rates (Le Devedec et al. 2012 ) are modulated by mechanical tension, which
comes either from the actomyosin contractility or from external forces applied to