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.

Definition of organ
A group of tissues that perform a specific
function or group of functions (www.biologyonline.org)

A differentiated part of an organism, such

as an eye, wing, or leaf, that performs a
specific function
(http://www.thefreedictionary.com/organ).

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 tissue 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
protein content.

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 strength.

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 in 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
proper

Areolar or
loose CT
kolagen, elastin

Dense CT
(fibrous CT)
ligaments &
tendons

Specialized
Connective tissue

Blood
Bone
Cartilage
Adipose
Reticular CT

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, and fluoride ions are also
present.

 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 to
be stretched.

 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;
osteoblasts for bone.

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 etiology, occurring predominantly
in young women.

 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 tdd 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
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 mjd sangat tdk larut
dan stabil.
Peny Sindroma Williams ( kel.
Perkembangan pd jar. 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
Peny Sindroma Marfan:
Mutasi gen u/ fibrilin, autosom dominan
Dislokasi lensa ( ektopia lentis)
Hiperekstensibilitas sendi, aracnodaktili,
dilatasi aorta desendens

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 bentuk
terurai

 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.

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

CELL ADHESION MOLECULES

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

Muscle tissue

Muscles contain 3 types

of protein fibers:

microfilaments,
microtubules, and
intermediate filaments

 Microfilaments are polymers

composed of globular unit monomers
called actin.
Microtubules are polymers composed
of two monomers, and tubulin.
These monomers contain the
nucleotide guanine instead of adenine.
They are involved in many cellular
processes including mitosis,
cytokinesis, and vesicular transport

 Intermediate filaments contain other

polymers such as keratin and don't
contain nucleotides in their monomers.
They compose structures inside cells but
are more familiar in external forms such
as hair, nails, horns and scales

Organization of Contractile Proteins in Muscle

Thick
Filament

Composed of hundreds of long, contractile myosin molecules

arranged in a staggered side by side complex.

Thin
Filament

Composed of a linear array of hundreds of globular, actin

monomers in a double helical. arrangement.

Sarcomere

The unit of contractile activity composed mainly of actin and

myosin and extending from Z line to Z line in a myofibril.

Myofibril

End to end arrays of identical sarcomeres.

Myofiber

A single multinucleate muscle cell containing all the usual cell

organelles plus many myofibrils.

Muscle

Organized arrays of muscle fibers.

Diagrammatic breakdown of a typical muscle. Shows how actin thin filaments and myosin thick filaments are arranged to form
the myofilaments of a sarcomere, continuing with the formation of myofibrils from many myofilaments.

Myofibril

Actin & myosin

 Myosin is one of the most abundant

proteins in the human body.
It is found in all the body's muscle
types, in the ears and eyes, in the blood
platelets, and is used in cytokinesis.
Because of all the diverse functions of
myosin, it can be grouped into
anywhere from seven to fourteen
unique categories. These categories
are grouped by the properties of the
head domains of the myosins.

 The most common type of myosin is

myosin class II. This is the type present
in muscle tissues.
Class II myosin is used to contract
muscle tissue, thereby giving an
organism mobility. Myosin II has this
function due to its complex
configuration. Myosin II also plays a role
enzymatically as it is an ATPase.
Myosin II is a component of the
myofibers in skeletal, smooth, and
cardiac tissue

Nervous Tissue
Supportive connective tissue cells
Neuroglia support and protect neurons
in the CNS. Specific glial cells are
phagocytes; others myelinate neuron
processes in the CNS or line cavities.
Schwann cells myelinate neuron
processes in the PNS

 Neurons
All neurons have a cell body containing
the nucleus and processes (fibers) of two
types; (1) axons (one per cell) typically
generate and conduct impulses away from
the cell body and release a
neurotransmitter, and (2) dendrites (one to
many per cell) typically carry electrical
currents toward the cell body.
Most large fibers are myelinated; myelin
increases the rate of nerve impulse
transmission.

Schwann cells myelinate neuron processes in the PNS

Bone Tissue

http://images.google.co.id/imgres?imgurl=http://chrischamcl.files.wordpress.com/2009/10/osteoporos

 Bone is formed through a lengthy

process involving ossification of a
cartilage formed from mesenchyme.
Two main forms of ossification occur in
different bones, intramembranous (eg
skull) and endochondral (eg vertebra)
ossification. Ossification continues
postnatally, through puberty until mid 20s

http://images.google.co.id/imgres?imgurl=http://www.roche.com/pages/facets/11/bone_remodelling2

http://kcampbell.bio.umb.edu/December01/Bone2.gif

 Osteoblasts manufacture bone and are

derived from mesodermal in origin, arising
from multipotential mesenchymal cells and
further differentiate into bone-lining cells
and osteocytes.
Osteoclasts resorb bone and are derived
from hematopoietic precursor cells formed
by the fusion of monocytic cells at the bone
sites to be resorbed.

 The marrow of bones is the site of

haematopoiesis, the generation of blood
cells. At birth nearly all bones are a
source of blood cells, this is restricted with
postnatal development to a few specific
bones. Pluripotential stem cells reside in
the marrow and are a self renewing
source of stem cells or commitment to a
progenitor cell.

Bone matrix and marrow

 The organic matrix of bone consists of:

95% Type I collagen
5% proteoglycans and noncollagenous
proteins (osteopontin and osteocalcin).

Epithelial Tissue

epithelium is a tissue composed of

cells that line the cavities and surfaces
of structures throughout the body.
Epithelium lines both the outside (skin)
and the inside cavities and lumen of
bodies. The outermost layer of our skin is
composed of dead stratified squamous,
keratinized epithelial cells.
http://en.wikipedia.org/wiki/Epithelial_tissue

Types of epithelium

Epithelial cells are often arranged in broad sheets or tubelike structures. Epithelium is commonly found on the
surfaces of the body and organs, and the lining of body
cavities, tubes, and ducts - the boundary between the
body's internal and external environments.

Epithelial tissues are physically separated from

underlying connective tissues by a basement
membrane (also called the basal lamina).

 Epithelial tissues contain no blood

vessels. Cells receive nourishment by
diffusion from a highly vascular area of
loose connective tissue just below the
basement membrane called the
lamina propria.
Epithelial tissues are derived from all
three primary germ cell layers:

 Ectoderm: The epithelial cells of the skin

and oral cavity (epidermis) are derived
from ectoderm. Epithelial cells covering
the cornea and lens, as well as sensory
receptors of the eyes, ears, and nose, are
also ectodermal in origin.
Mesoderm: The epithelial lining of blood
vessels (endothelium) is derived from
mesoderm. The epithelial lining of the
pleural and peritoneal cavities
(mesothelium) also originate from
mesodermal cells.

 Endoderm: The epithelial lining of the

respiratory system and digestive tracts
- as well as the functional cells
(parenchyma) of the liver, pancreas,
gallbladder, thyroid, and parathyroid,
are derived from endoderm.

Functions

Barrier
Absorption
Secretion
Sensory
Contractility

Adipose Tissue

 Adipose tissue or fat is loose

connective tissue composed of
adipocytes. Its main role is to store
energy in the form of fat, although it also
cushions and insulates the body
Two types of adipose tissue exist:
white adipose tissue (WAT) and
brown adipose tissue (BAT).

Brown adipose tissue

Adipose tissue with microvessels

 Adipose tissue also serves as an

important endocrine organ by producing
recently-discovered hormones such as
leptin, resistin and the cytokine TNF.
The formation of adipose tissue appears
to be controlled by the adipose gene.

Subcutaneous adipose tissue