Healthcare and Medicine Reference
In-Depth Information
Fig. 1.69 Two views of the relationship between the cell and the surrounding ECM. (A) The traditional view, in which each element has
its autonomy. (B) The more current view, in which the nuclear material, nuclear membrane, and cytoskeleton are all mechanically linked
via the integrins and laminar proteins to the surrounding ECM. (Reproduced with kind permission from Oschman 2000.)
By the early 1980s, it was understood in scientific
circles that the ground substance and adhesive matrix
proteins were linked into the system of the intracellular
cytoskeleton."' It is that linkage - from the nucleus to
the cytoskeleton to the focal adhesion molecules inside
the membrane, through the membrane with the integ-
rins, and then via the proteoglycans such as fibronectin
to the collagen network itself (Fig. 1.70) - which is
extraordinarily strong in the MFBs, working generally
from the cell out onto the matrix, but the same kind of
mechanoregulatory process extends to every cell, often
working from the outside in: movements in the mechan-
ical environment of the ECM can affect, for better or
worse, how the cell functions.
While it is obvious that some kind of cell adhesion is
necessary to hold the body together, the extent and
importance of this mechanical signaling, now called
mechanotransduction, is being seen to have a role in a
wide variety of diseases, including asthma, osteoporo-
sis, heart failure, atherosclerosis, and stroke, as well as
the more obvious mechanical problems such as low
back and joint pain. 11 3 'Less obviously, it helps to direct
both embryonic development and an array of processes
in the fully formed organism, including blood clotting,
wound healing, and the eradication of infection.' 11411 5
For instance:
A dramatic example of the importance of adhesion to
proper cell function comes from studies of the interaction
between matrix components and mammary epithelial
cells. Epithelial cells in general form the skin and lining
of most body cavities; they are usually arranged in a
single layer on a specialized matrix called the basal
lamina. The particular epithelial cells that line the
mammary glands produce milk in response to hormonal
stimidation. If mammary epithelial cells are removed
from mice and cultured in laboratory dishes, they quickly
lose their regular, cuboidal shape and the ability to make
milk proteins. If, hoioever, they are grown in the presence
of laminin (the basic adhesive protein in the basal
Fig. 1.70 The integrins - 'floating' in the phospholipid membrane
- make Velcro®-like connections between the cellular elements
shown in Figure 1.68 and the extracellular elements of the ECM.
lamina) they regain their usual form, organize a basal
lamina, and assemble into gland-like structures capable
once again of producing milk components. 116
In other words, the mechanical receptors and the pro-
teins of the ECM are linked into the cell in a communi-
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