TISSUE BIOCHEMISTRY &

EXTRACELLULAR MATRIX

Abdul Salam M. Sofro & Yulia

S
Faculty of Medicine
YARSI University
Definition of tissue

An aggregation of
morphologically similar cells and
associated intercellular matter
acting together to perform one
or more specific functions in the
body.
Extracellular matrix (ECM) : any
substance produced by cells and
excreted to the extracellular space
within the tissues, serving as a
scaffolding to hold tissues together
and helping to determine their
characteristics (http://medical-
dictionary.Thefreedictionary.Com/e
xtracellular+matrix)
 Extracellular matrix (ECM) : any
material produced by cells and
secreted into the surrounding
medium, but usually applied to the
noncellular portion of animal
tissues (http://www.biology-
online.org/dictionary/Extracellular_
matrix)
Definition of organ

A group of tissues that perform a

specific function or group of
functions (www.biology-online.org)
A differentiated part of an organism,
such as an eye, wing, or leaf, that
performs a specific function
(http://www.thefreedictionary.com/o
rgan).
Widely distributed tissues

Connective tissue
Muscle tissue
Nervous tissue
Epithelial tissue
Bone tissue
Adipose tissue
There are four basic types of
tissue: muscle, nerve,
epidermal, and connective.
Connective tissue
Traditional classification of tissue
Connective tissue
Connective tissue proper
Specialized Connective tissue:
Epithelial tissue
Muscle tissue
Nervous tissue
 Connective tissue

is one of the four types of tissues in

traditional classifications (the others
being epithelial, muscle, and nervous
tissue)
All or most tissues in this category are
similarly:
Involved in structure and support.
Derived from mesoderm, usually.
Characterized largely by the traits of
non-living tissue.
 Blood, cartilage, and bone are
usually considered connective
tissue, but because they differ so
substantially from the other tissues
in this class, the phrase "connective
tissue proper" is commonly used to
exclude those three.
Collagen is the main protein of
connective tissue in animals and the
most abundant protein in mammals,
making up about 25% of the total
Classification

Connective tissue proper

Areolar (or loose) connective tissue
holds organs and epithelia in place,
and has a variety of proteinaceous
fibres, including collagen and
elastin.
Dense connective tissue (or, less
commonly, fibrous connective
tissue) forms ligaments and
tendons. Its densely packed
collagen fibers have great tensile
Specialized connective tissues
Blood functions in transport. Its
extracellular matrix is blood
plasma, which transports dissolved
nutrients, hormones, and carbon
dioxide in the form of bicarbonate.
The main cellular component is red
blood cells.
Bone makes up virtually the entire
skeleton in adult vertebrates.
 Cartilage makes up virtually the
entire skeleton chondrichthyes. In
most other vertebrates, it is
found primarily in joints, where it
provides cushioning. The
extracellular matrix of cartilage is
composed primarily of collagen.
Adipose tissue contains
adipocytes, used for cushioning,
thermal insulation, lubrication
(primarily in the pericardium) and
energy storage [fat]
 Reticular connective tissue is a
network of reticular fibers (fine
collagen, type III) that form a soft
skeleton to support the lymphoid
organs (lymph nodes, bone
marrow, and spleen.)
Embryonic connective tissues
Mesenchymal connective tissue
Mucous connective tissue
 CONNECTIVE TISSUE

Connective tissue Specialized

proper Connective tissue

Areolar or loose
CT kolagen, Blood
elastin Bone
Cartilage
Dense CT Adipose
(fibrous CT) Reticular CT
ligaments &
tendons
Other classification of connective
tissue
Supporting connective tissue
(Gives strength, support, and
protection
to the soft parts of the body)
Cartilage. Example: the outer ear
Bone. The matrix of bone contains
collagen fibers and mineral
deposits. The most abundant
mineral is calcium phosphate,
although magnesium, carbonate,
 Binding connective tissue
(It binds body parts together)
Tendons connect muscle to
bone. The matrix is principally
collagen, and the fibers are all
oriented parallel to each other.
Tendons are strong but not
elastic.
Ligaments attach one bone to
another. They contain both
collagen and also the protein
elastin. Elastin permits ligaments
 Fibrous connective tissue
(It is distributed throughout the
body. It serves as a packing and
binding material for most of our
organs. Collagen, elastin, and other
proteins are found in the matrix).
Fascia is fibrous connective
tissue that binds muscle together
and binds the skin to the
underlying structures. Elastin is
a major protein component.
 Adipose tissue is fibrous
connective tissue in which the cells,
called adipocytes, have become
almost filled with oil. Fibrous and
binding connective tissue is derived
from cells called fibroblasts, which
secrete the extracellular matrix.
Note: The extracellular matrix of
cartilage and bone is secreted by
specialized cells derived from
fibroblasts:
chondroblasts for cartilage;
Disorders of connective tissue
Various connective tissue conditions have been
identified (can be both inherited and
environmental)

Marfan syndrome - a genetic disease

causing abnormal fibrillin
Scurvy - caused by a dietary deficiency in
vitamin C, leading to abnormal collagen.
Ehlers-Danlos syndrome - deficient type
III collagen- a genetic disease causing
progressive deterioration of collagens,
with different EDS types affecting
different sites in the body, such as joints,
heart valves, organ walls, arterial walls,
etc.
 Loeys-Dietz syndrome - a genetic
disease related to Marfan syndrome,
with an emphasis on vascular
deterioration.
Pseudoxanthoma elasticum - an
autosomal recessive hereditary
disease, caused by calcification and
fragmentation of elastic fibres,
affecting the skin, the eyes and the
cardiovascular system.
Systemic lupus erythematosus - a
chronic, multisystem, inflammatory
disorder of probable autoimmune
 Osteogenesis imperfecta (brittle
bone disease) - caused by insufficient
production of good quality collagen
to produce healthy, strong bones.
Fibrodysplasia ossificans progressiva
- disease of the connective tissue,
caused by a defective gene which
turns connective tissue into bone.
Spontaneous pneumothorax -
collapsed lung, believed to be related
to subtle abnormalities in connective
tissue.
Sarcoma - a neoplastic process
originating within connective tissue.
Extracellular matrix

Collagens
Elastin
Proteoglycans &
glycosaminoglycans (GAGs)
Cell-adhesion molecules
(fibronectin, laminin, others)
Cell Membranes and Extracellular Matrix (ECM)
www.recoveryeq.com/recovery_eq_technical_mono...
Komponen utama
Protein struktural ( kolagen,
elastin, fibrilin.)
Protein khusus (fibrillin,
fibronektin, laminin)
Berbagai proteoglikan ( yg terdiri
atas rantai panjang disakarida yg
berulang/ glikosaminoglikan)
 Kolagen
Komponen utama pembentuk jaringan
ikat.
Terdapat +/- 19 tipe kolagen yg
berbeda dan tersusun dari +/- 30
rantai polipeptida yg berlainan
Struktur kolagen: ( Gly-X-Y)n, dimana
1/3nya ditempati asam amino Glisin
+/- 100 aa X adalah Prolin
+/- 100 aa Y adalah hidroksiprolin
Prolin dan hidroksiprolin memberikan
sifat rigiditas pd molekul kolagen
 Kolagen cont.

Berbentuk triple heliks : 3 rantai

polipeptidanya terpilin spt tali
Jenis kolagen: ada 7-8 jenis gen
rantai polipeptida ( 1 (I), 2, 1
(II), 1(III), 1(IV), 1 (V), 2 (V).
 Molecular biology of Collagen, a major structural protein

Figure 2000 by Griffiths et al.; All text material 2005 by Steven M. Carr
Elastin
Bertanggungjawab atas sifat mulur
dan mengkerut scr elastis dlm
suatu jaringan
Bentuknya berupa gelungan acak
Tdp pd paru, pembuluh drh arteri
besar, bbrp ligamnetum.<< kulit
dan kartilago telinga
Hanya ada 1 tipe genetik untuk
elastin
Elastin
Tidak terdapat struktur berulang
Tidak mengandung KH, maupun
AA Hidroksilisin.
Setelah terjadi ikatan silang dlm
bentuk ekstraselnya, elastin
menjadi sangat tdk larut dan
stabil.
Peny Sindroma Williams
(kelainan perkembangan pd
jaringan ikat dan SSP)
www.biomed.metu.edu.tr/.../image008.gif
Fibrilin
Sebuah glikoprotein berukuran
besar ( 350 KDa) yg merupakan
komponen struktural mikrofibril.
Disekresikan oleh fibroblas
Penyakit Sindroma Marfan:
Mutasi gen u/ fibrilin, autosom
dominan
Dislokasi lensa (ektopia lentis)
Hiperekstensibilitas sendi,
arachnodaktili, dilatasi aorta
Fibronectin
Adalah protein yang
menghubungkan sel dengan serabut
kolagen di matriks ekstrasel,
memungkinkan sel bergerak di
matriks ekstrasel.
Fibronectin mengikat kolagen dan
integrins permukaan sel,
menyebabkan reorganisasi
sitoskeleton sel dan memfasilitasi
pergerakan sel.
Fibronectins disekresi oleh sel dalam
 Bila mengikat integrins molekul
fibronectin terbuka sehingga dapat
membentuk dimer dan berfungsi.
Fibronectins juga membantu di
tempat jejas dengan mengikat
trombosit selama penggumpalan
darah dan memfasilitasi pergerakan
sel ke area yang terkena selama
penyembuhan luka.
Laminin
Adalah protein yang dijumpai di
lamina basal semua hewan
Laminin membentuk jejaring
seperti struktur jaring yang
menahan daya tarik di lamina
basal.
Juga membantu dalam adhesi sel
dan mengikat komponen matriks
ekstrasel lain seperti kolagen,
nidogen dan entactin.
 Proteoglikan

Merupakan protein yang

mengandung glikosaminoglikan
dgn ikatan kovalen (sindekan,
betaglikan, agrekan dll)
Pada matriks ekstraseluler
berikatan baik dengan kolagen
maupun elastin.
Sel-sel Mammalia mampu
menghasilkan 40 jenis
proteoglikan. Molekul ini dapat
bertindak sebagai pengatur
jaringan, dan mempengaruhi
berbagai macam aktivitas sel,
misalnya sebagai adhesi dan
aktivasi faktor pertumbuhan.
Unit dasar proteoglikan tersusun
atas core protein yang
ditempeli glicosaminoglikan
secara kovalen
Glikosaminoglikan
Glikosaminoglikan : polisakarida
tak bercabang yg tersusun dari
mol. Disakarida berulang dimana
salah satu komponennya selalu AA.
As. Hialuronat, kondroitin sulfat,
keratan sulfat I dan II, heparin,
heparan sulfat, dermatan sulfat)
Peny Mukopolisakaridosis
Interaksi antara Sel dan Matriks ekstrasel

Matriks ekstrasel adalah jalinan kuat yang

mengandung proteoglikan terkait dengan
collagen, elastin, dan fibronectin.
Fibronectin, memiliki beberapa ranah
terpisah yang mengikat fibrin, heparan
sulfate, collagen & protein membran plasma
yang disebut integrins.

Integrin memediasi isyarat antara interior sel & matriks ekstrasel. Interaksi ini
tak hanya menancapkan sel di matriks ekstrasel, tetapi juga memberi jalur yg
mengarahkan migrasi sel pada jaringan yg sedang tumbuh dan
mengantarkan informasi dua arah sepanjang membran plasma.
Cell adhesion molecules (CAM)

Kebanyakan CAMs termasuk dalam

4 keluarga protein: Ig
(immunoglobulin) superfamily
(IgSF CAMs), integrins, cadherins
dan selectins.