Essential Cell Biology 5th edition

ECB5 e20.11-20.11
Extracellular Matrix and Connective Tissues
697
decorate the surface of collagen fibrils and link the fibrils to one another
and to other components in the extracellular matrix.
The connective-tissue cells that manufacture and inhabit the extracellular
matrix go by various names according to their tissue type: in skin,
tendon, and many other connective tissues, they are called fibroblasts
(see Figure 20–9); in bone, they are called osteoblasts. These cells make
both the collagen and the other macromolecules of the matrix. Almost
all of these molecules are synthesized intracellularly and then secreted
in the standard way by exocytosis (discussed in Chapter 15). Outside the
cell, they assemble into huge, cohesive aggregates. If assembly were to
occur prematurely, before secretion, the cell would become choked with
its own products. In the case of collagen, the cells avoid this catastrophe
by secreting collagen molecules in a precursor form, called procollagen,
which has additional peptide extensions at each end that obstruct
premature assembly into collagen fibrils. Extracellular enzymes—called
procollagen proteinases—cut off these terminal extensions to allow
assembly only after the molecules have emerged into the extracellular
space (Figure 20–10).
Some people have a genetic defect in one of the extracellular proteinases,
so that their collagen fibrils do not assemble correctly. As a result,
their connective tissues have a lower tensile strength and are extraordinarily
stretchable (Figure 20–11).
Cells in tissues have to be able to degrade extracellular matrix as well as
make it. This ability is essential for tissue growth, repair, and renewal;
it is also important where migratory cells, such as macrophages, need
to burrow through the thicket of collagen and other matrix polymers.
Matrix proteases that cleave extracellular proteins play a part in many
disease processes, ranging from arthritis, where they contribute to the
breakdown of cartilage in affected joints, to cancer, where they help cancer
cells invade normal tissue.
Cells Organize the Collagen They Secrete
To do their job, collagen fibrils must be correctly aligned. In skin, for
example, they are woven in a wickerwork pattern, or in alternating layers
with different orientations so as to resist tensile stress in multiple directions
(Figure 20–12). In tendons, which attach muscles to bone, they are
aligned in parallel bundles along the major axis of tension.
The connective-tissue cells that produce collagen control this orientation,
first by depositing the collagen in an oriented fashion and then by
rearranging it. During development of the tissue, fibroblasts work on the
collagen they have secreted, crawling over it and pulling on it—helping
to compact it into sheets and draw it out into cables. This mechanical
role of fibroblasts in shaping collagen matrices has been demonstrated
dramatically in cell culture. When fibroblasts are mixed with a meshwork
of randomly oriented collagen fibrils that form a gel in a culture
dish, the fibroblasts tug on the meshwork, drawing in collagen from
their surroundings and compacting it. If two small pieces of embryonic
tissue containing fibroblasts are placed far apart on a collagen gel, the
QUESTION 20–2
Mutations in the genes encoding
collagens often have detrimental
consequences, resulting in severely
crippling diseases. Particularly
devastating are mutations that
change glycines, which are required
at every third position in the
collagen polypeptide chain so that it
can assemble into the characteristic
triple-helical rod (see Figure
20–9). Would you expect collagen
mutations to be detrimental if only
one of the two copies of a collagen
gene is defective?
procollagen
secretory vesicle
secreted procollagen molecule
collagen molecule
PROCOLLAGEN
PROTEINASE CLEAVES
TERMINAL
PROCOLLAGEN
EXTENSIONS
Figure 20–10 Procollagen precursors are cleaved to form mature
collagen outside the cell. Collagen is synthesized as a procollagen
molecule that has unstructured peptides at either end. These peptides
prevent collagen fibrils from assembling inside the fibroblast. When the
procollagen is secreted, extracellular procollagen proteinases remove
its terminal peptides, producing mature collagen molecules. These
molecules can then self-assemble into ordered collagen fibrils (see also
Figure 20–9).
10–300
nm
SELF-ASSEMBLY
INTO FIBRIL
collagen fibril