2. Background
• The main biopolymer in animals is the protein collagen
• It makes impressively strong structures, including cartilage and bone
• Cell surface adhesion proteins enable cells to establish intimate
relationships with each other and macromolecules in the extracellular
matrix
• Fibroblasts synthesize and secrete the macromolecules that form the
extracellular matrix
• Specialized phagocytic cells and immune system cells patrol the
extracellular matrix
3. Cells of the Extracellular Matrix
• A remarkable variety of specialized cells populate the connective
tissues
• These cells manufacture extracellular matrix, defend against infection,
and maintain energy stores in the form of lipid
• These indigenous cells are specialized: Fibroblasts make the collagen,
elastic fibers, and proteoglycans of the extracellular matrix
• Fat cells store lipids, chondrocytes secrete the matrix for cartilage;
and osteoblasts manufacture the calcified matrix of bone
• The remaining cells arise elsewhere
5. Indigenous Connective Tissue Cells
• Mesenchymal cells resemble fibroblasts but with fewer organelles
• The nature of the mesenchymal stem cells in adult tissues is still being
investigated
• Fibroblasts are the, connective tissue workhorses
• Mature fibroblasts have abundant rough endoplasmic reticulum and a large
Golgi apparatus
• They are generally spindle-shaped, with a flattened, oval nucleus
6. Indigenous Connective Tissue Cells
White Fat Cells
• Adipocytes store lipids as a readily accessible reserve of energy
• They arise from mesenchymal progenitors and are distributed in
connective tissues beneath the skin and in the abdominal mesentery
• These round cells vary in diameter depending on the size of their
single, large, lipid droplet
• Fat cells respond to the metabolic needs of the body, also an
endocrine organ
8. Extracellular Matrix Molecules
• The extracellular matrix is composed of only five classes of
macromolecules— collagens, elastin, proteoglycans, hyaluronan, and
adhesive glycoproteins
• The extracellular matrix in different tissues is adapted to particular
functional requirements
• Beyond providing mechanical support, the extracellular matrix also strongly
influences embryonic development, provides pathways for cellular
migration, provides essential survival signals, and sequesters important
growth factors.
9.
10. Extracellular Matrix Molecules
• The collagen family is the most abundant and versatile classes of
proteins in the human body
• Collagens form a wide range of different structures with remarkable
mechanical properties
• The defining feature of collagens is a rod-shaped domain composed
of a triple helix of polypeptides
• Rubber-like elastic fibers are found throughout the body and are
prominent in the connective tissue of skin, the walls of arteries and
the lung
11.
12. Extracellular Matrix Molecules
Glycosaminoglycans and Proteoglycans
• Glycosaminoglycans are long polysaccharides made up of repeating
disaccharide units
• Proteoglycans vary in structure and function, but their associated
GAGs confer some common features.
• Most are secreted into the extracellular matrix, where they are major
constituents of cartilage, loose connective tissue, and basement
membranes
13.
14. Adhesive Glycoproteins
• Adhesive glycoproteins are more than molecular glue; they also
provide cells with signals required for the development and repair of
tissues.
• Cells receive these signals when they bind to the matrix components.
• Adhesive glycoproteins provide specific molecular interactions in the
matrix by binding to cells, matrix macromolecules, or both
• Adhesive proteins with multiple binding sites for cell surface
receptors link cells together. For example, fibrinogen aggregates
platelets during blood clotting
• Fibronectin mediates the attachment of cells to fibrin and collagen
15.
16. Basal Lamina
• The basal lamina, a thin, planar assembly of extracellular matrix
proteins, supports all epithelia, muscle cells, and nerve cells
• This two-dimensional network of protein polymers forms a
continuous rug under epithelia and a sleeve around muscle and nerve
cells.
• It can act as semipermeable filters for macromolecules,
• Collagens type VI, VII, XV, and XVIII connect the lamina to the
underlying connective tissue
17.
18. Matrix Metalloproteinases
• Many physiological processes depend on the controlled degradation
of the extracellular matrix
• Conversely, uncontrolled destruction of extracellular matrix
contributes to degenerative diseases
• Many of these enzymes cleave and release biologically active
fragments from matrix or membrane proteins.
• Zn-dependent proteases account for both the physiological and
pathological degradation of diverse extracellular matrix and cell
surface proteins
• The first class is called matrix metalloproteinases (MMPs)
Remarkably, just four families of plasma membrane adhesion proteins, immunoglobulin cell adhesion molecules (IgCAMs), cadherins, integrins, and selectins, account for much of cellular adhesion
The migratory patterns of the fibroblasts determine the patterns of collagen fibrils in tissues
In response to tissue damage, fibroblasts proliferate and migrate into the wound, where they synthesize new matrix to restore the integrity of the tissue
This process can get out of control if inflammatory cells secrete excessive transforming growth factor (TGF)-β and other factors that stimulate fibroblasts to produce matrix molecules
Fibrosis, excess accumulation of extracellular matrix, can compromise the functions of the heart, liver, lung, or skin
containing triglycerides, neutral lipids with a fatty acid esterified to all three carbons of glycerol
. After a meal, parasympathetic nerves stimulate fat cells to take up fatty acids and glycerol from blood and synthesize triglycerides for storage. During fasting or when the body requires energy, sympathetic nerves acting through β-adrenergic receptors (see Fig. 27.3), stimulate adipocytes to hydrolyze fatty acids from triglycerides for release into the blood for use by other organs. If a mammal ingests excess calories, white fat cells enlarge their lipid stores and increase in number. White fat cells are long lived, with a half-life approximately 9 years, so the excess cells persist in obese individuals
which vary widely in tendons, blood vessel walls, cartilage, bone, the vitreous body of the eye, and subcutaneous fat
They are entropic springs that recoil passively after tissues are stretched
Energy stored in elastic fibers pushes blood through the circulation between heartbeats.
Elastic fibers are composite materials; a network of fibrillin microfibrils is embedded in an amorphous core of crosslinked elastin, which makes up 90% of the organic mass
A third protein, called fibulin, is required for elastin subunits to assemble between the microfibrils
Of the known GAGs, hyaluronan (formerly called hyaluronic acid) is exceptional
First, enzymes on the cell surface synthesize the alternating polymer of [D-glucuronic acid β (1 → 3) D-N-acetyl glucosamine
Second, hyaluronan is not modified postsynthetically, as are all other GAGs
A third group of adhesive proteins links matrix macromolecules together. For instance, nidogen attaches laminin to collagen and link protein attaches aggrecan-proteoglycan to hyaluronan
Heterodimeric transmembrane receptors called integrins bind most adhesive glycoproteins that interact with cells
Establishing the biological functions of adhesive glycoproteins is challenging because of their overlapping functions and large sizes
The basal lamina and associated collagen fibrils form the “basement membrane” that is observed in histologic preparations of epithelia
Although many proteins contribute to the stability of the basal lamina (Fig. 29.18), only the adhesive glycoprotein laminin is essential for the initial assembly of basal laminae during embryogenesis
MMP activity is carefully regulated at three levels, normally restricting proteolysis to sites of tissue remodeling or physiological breakdown. First, only particular connective tissue, inflammatory, and epithelial cells are genetically programmed to express MMP genes and to respond to growth factors and cytokines to increase production under appropriate circumstances. Second, autoinhibited MMPs on the cell surface require propeptide cleavage for activation. Proteolytic cleavage and dissociation of the propeptide activate the enzyme. Cellular movements then deliver the active protease to specific substrates.
