1. collagens
2. elastin
3. pretoglycans
4. hyaluronan
5. adhesive glycoprotein

1. mechanical support
2. secrete growth factor
3. pathways for cellular migration
4. influence embryonic development
5. cell survival, proliferation, shape and function

ECM secreted by fibroblast

Bone secreted by Osteoblast

Cartilage by chondrioblast

1. rich in glycine (fx pack 3 alpha chains), and proline (stabilize each alpha chain)
2. 25 alpha chains>> various combinations>> about 20 major types of collagen

1. collagen I: bone, tendon, ligament, skin, dentin
2. collagen II: hyaline cartilage, vitreous body
3. Collagen III: skin, blood vessels
4. Collagen V: fetal membranes, skin, bone, placenta, synovial membrane.
5. Collagen XI

>>synthesized in rough ER.

1. pro alpha chain synthesized
2. hydroxylation of proline and lysin
3. glycosylation of selected hydroxylysin
4. self-assembly of 3 pro alpha chain
5. pro-collagen triple-helix formed
6. secretion
7. cleavage of propeptide>collagen molecules (tropocollagen)
8. self-assembly into fibril
9. fibril aggregate into collagen fibers.

• collagen fibrils resist tensile force. ex. skin wowen in wickerwork pattern, tension in parallel pattern, bone in plywood pattern
• size and arrangment of collagen fiber determined by connective tissue cell in 2 ways: 1)regulate deposition of collagen molecule. 2) influence organization of collagen fiber by secreting along with matrix macromolecules.
• fibroblast interact with collagen they secreted by crawling over it and tugging on it into sheet and cable.
• fibroblast influece alignment of collagen, collagen on the other hand determine distribution of fibroblast.

• rubber like, provide elasticity
• ONLY in embryonic and juvenile fibroblast that synthesize elastic fiber. adult tissue becomes less elastic with age. lost of elastin in skin cause wrinkle.
• component:

hydrophobic protein rich in P and G

not glycosylated

no hyroxylysin

alternating hydrophobic segment and alanine and lysin rich alpha segment (form x-link between adjacent molecule)

• tropoelastin secreted into extracellular space
• tropoelastin assembled >> elastic fiber in plasma membrane folding.
• tropoelastin x-link between lysine residues>> net work of elastin fibers and sheets.
• x-linked elastin covered microfibril with microfibril associated glycoprotein (MAGPs) include fibrillin I and fibrillin II.

Mutation in elastin>> narrowing aorta

mutated fibrillin I>> Marfan's syndrom

• Elastin woven with inelastic to limit extent to stretching and prevent tissue tearing.
• help to reverse tissue back to original state after mechanical deformation.

Loose connective tissue:

collagen (tensile strength)

elastin (resilience)

reticular fiber (joining)

2 type of LCT: fibroblast and macrophage

has great tensile strength

tendon and ligament

1. protein linked with glycosaminoglycan (GAGs)
2. produce highly hydrated, gel-like "ground substance" in which collagen and elastin are embedded.
3. resist compressive force but allow rapid diffusion of nutrients, metabolites and hormones.
4. distringuish by core protein and arrangement of sugar side chain

• core protein synthesized in rER
• GAGs are put on core protein in golgi
• tetrasacchride first attached to seerine side chain on core protein, then anchors dermatin sulfate, chondroitin sulfate and heparan sulfate.
• aggrecan proteoglycan= large 3E6 dalton>>cartilage
• decorin proteoglycan= small>> decorate surface of collagen fibril.
• periecan proteoglycan= making basement membrane

• secreted into ECM becomes substitution of cartilage, loose connective tissyem and basement membrane
• some are integral component of plasma membrane
• have core protein inserted across lipid bilayer>>act as receptors collaborate with conventional cell surface receptor protein. ex. syndecans can bind fibroblast grow factors (FgFs) and present them to FGF receptor protein

• provide hydrated space around and between cell. ex. form gels of varying pore size, selective filers for molecule base on size and charge.
• proteoglycan>chemical signaling, bind secreted signal molecules such as grow factor. can enhance or inhibit signal.
• transforming growth factor beta (TGF beta) bind to decorin which inhibits growth factor
• proteoglycan also bind, regulate activities of proteases, and protease inhibitors
• proteoglycan can control activity of secreted protein

1. immobilize protein close to where it is product, thus restrict range of action
2. sterically block activity of protein
3. sterically block activity of protein for delayed release
4. protect protein from pretolytic degradation
5. alter concentration

• simplest, larges GAGs repeated nonsulfate dissacharide.
• play role of space filler during embryonic development
• synthesized from basal side of epithelium: serve to create a cell free space into wich cell migrates (ex. cornea). when cell migration ends, excess hyaluronan degrade by hyaluronidase

• spin out directly from cell surface on a complex embedded in plasma membrane, not modified postsynthetically.

• resist compressive force in tissue and joints
• produce large quantity during wound healing
• serve as lubricant in joint fluid
• wharton's jelly (connective tissue in embryo) is hyallluran provide resistant to compression of 2 umbilical arteries and umbilical vein

• contribute to organizing ECM, help cell attach to it. Multiple domain specific for macromolecule (collagen, heparin) and for receptor on surface of cell.
• adhesive glycoprotein serve as mediators between matrix, macromolecules and associated cell.

• large glycoprotein imporant to cell adhesion to matrix and guilding all migration in embryo
• has 2 subunits jointed by 2 disulfide bonds
• type III fibronectin repeat binds intefrin
• RGD (arg, gly, asp) tripeptide sequence are recognized  by several mem of intefrin family.

encoded by single large gene

• plasma fibronectin: soluble, circulate in blood
• tissue fibronectin: highly insoluble.

fibronectin assemble into fibrils by fibronectin-binding-integrin

• fibronectin fibrils >> align with adjacent intracellular actin stress fiber. uteroglobin prevents fibronectins to form fibrils in kidney

tissue fibronectin: glue cell to fibrous membrane of ECM

plasma fibronectin: enhance blood clot, wound heal, phagocytosis

• major component of basal lamina.
• consists of 3 disulfide-linked polypeptide chains designated alpha, beta, and gamma chains. variants for each chain give rise to several laminin isoforms with different structure and function.
• have binding sites for cell surface receptors (integrin), type IV collagen, and other adhesion proteins
• laminin monomers self associate to form a network that is part of the basal lamina.
• Basal lamina provides a scaffold for the original tissue architecture.

• important during process such as cell migration in response to infection and tissue damage, tissue remodeling during embryogenesis, wound healing and involution of uterus afer childbirth.
• ECM degraded by 3 types:

1. matrix metalloprotease (MMPs)
2. serine proteases

the action of proteases is restricted by protease inhibitors:

1. tissue inhibitor of metalloprotease (TIMPs)
2. serine protease inhibitor (serpins)

• intracellular actin filaments influence the orientation of the ECM proteins, include tissue fibronectin
• ECM molecules organize the cell cytoskeleton
• surface receptors (integrins) mediate the interactions between cell cytoskeleton and ECM components

• the outcome of the repair process is dependent on a balance between ECM degradation and synthesis
• MMPs and thier inhibitors (TIMPs) are spatially and temporally regulated during healing prcess and requires the controlled remodeling of the ECM