Biomedical Engineering Reference
In-Depth Information
Chapter 9
Matrices
9.1 Biological Introduction
As already seen in Chapter 5, cell migration on and within tissues plays a
critical role in a diverse array of processes, such as in developing embryos,
where the coordinated movement of cells of different origin along ECM layers
is crucial for organogenesis, and migratory defects at all stages lead to severe
embryonic malformations [220]. In adult organisms, cells are normally qui-
escent, except in immune surveillance or inflammation, where leukocytes ac-
tively migrate from blood vessels into infected tissues and then into the lymph
node for effector functions [145], and in wound healing, where migration con-
tributes to the repair of both basement membrane-underlaid epithelium and
connective tissues. In pathological conditions, cell migration is involved in
chronic inflammatory diseases such as atherosclerosis, or in cancer cell inva-
sion into ECM and metastatization [337]. The process of cell migration is
finally exploited in biomedical engineering applications for the regeneration of
various tissues, such as cartilage, skin, or peripheral nerves in vivo or in vitro
[63, 178, 373, 418].
Cell motile behavior is modulated by a spatiotemporally integrated set
of multilevel mechanisms that are influenced not only by the biochemistry
of extracellular and intracellular signaling, but also by the biophysics of the
surrounding environment, whose basic component is the extracellular matrix
(ECM). The ECM forms, in fact, the architecture of a number of structures,
i.e., two-dimensional (2D) flat basement membranes, or three-dimensional
(3D) connective tissues and can be described as a complex network of insoluble
structural fibrous proteins such as collagen type I, and soluble glycosaminogly-
cans and glycoproteins, that together provide microstructural guidance cues
and biochemical stimuli for moving individuals.
How does a cell migrate then on and in ECMs? For the basic program of cell
migration over flat ECM substrates, four requirements have been identified.
Migrating cells
1. Are morphologically polarized in the direction of motion.
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