Biomedical Engineering Reference
In-Depth Information
sive dots results in limited cell attachment and spreading, and dramatically
reduced the formation of focal adhesion and actin stress fibres. The range
between 58-73 nm was proposed to be a universal length scale for integrin
clustering and activation, since these properties were found to be shared by
avarietyofculturedcells.
Furthermore, the pliability of the matrix providing adhesive ligands and
the anchorage of the matrix to the environment was shown to determine
the variant of cell-matrix adhesion developing by embedded cells which, in
turn, may control their fate transitions (for an example see also Sect. 4.1).
Cukierman et al. [45, 46] could convincingly show that based on a similar
collagen-based network the 2D vs. 3D microstructure and their mechanical
characteristics strongly influence the character of cell-matrix adhesions: The
composition and function of adhesions in three-dimensional (3D) matrices
derived from tissues or cell culture were found to differ substantially from
focal and fibrillar adhesions characterized on 2D substrates in their content
of
α
V
β
3
integrins, paxillin, other cytoskeletal components, and ty-
rosine phosphorylation of focal adhesion kinase. Relative to 2D substrates,
3D-matrix interactions were also reported to display enhanced activities and
narrowed integrin usage. These distinctive in vivo 3D-matrix adhesions were
demonstrated to differ in structure, localization, and function from classically
described in vitro adhesions, and concluded to be more biologically relevant
to living organisms.
Recently, the behavior of some cells on soft materials was found to be char-
acteristic of important phenotypes. Discher et al. [47, 48] reported important
facts to clarify how tissue cells—including fibroblasts, myocytes, neurons,
and other cell types—sense matrix stiffness based on quantitative studies of
cells adhering to gels (or to other cells) with which elasticity can be tuned
to approximate that of tissues. Contractile myocytes were reported to sense
their mechanical as well as molecular microenvironment, altering expres-
sion, organization, and/or morphology accordingly. The cells were cultured
on collagen strips attached to glass or polymer gels of varied elasticity. Subse-
quent fusion into myotubes was found to occur independent of the substrate
flexibility. However, myosin/actin striations emerged later only on gels with
stiffness typical of normal muscle (passive Young's modulus approximately
12 kPa). On glass and on much softer or stiffer gels cells did not striate. Unlike
sarcomere formation, adhesion strength was found to increase monotonically
versus substrate stiffness with strongest adhesion on glass.
While the above-cited studies mainly revealed the impact of physical char-
acteristics of ECM structures on cells grown in culture it seems justified to
conclude that various kinds of microstructures occurring in natural matrix
variants may act in similar ways. This holds particularly true for the guidance
of cells with respect to growth in a certain orientation of larger ensembles
as occurring in the formation—or conservation—of segmented structures in
various tissues [49-52]. However, the wealth of in vivo data available on the
α
5
β
1
and
