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CELL MEMBRANE &

CYTOSKELETON
Carmen Lpez M.D.
Hematologist
Introduction
Cell are the basic structural and functional Cytoplasm
units of all multicellular organisms
They use the same kinds of molecules to engage in
contraction, and they duplicate their genetic material in the
same manner.
Nucleus

The Cell can be divided in two major


compartments: Cytoplasm & nucleus

Cytoplasm contains organelles and inclusions


in an aqueous gel (cytoplasmic matrix).
This consist of a variety of solutes including inorganic
ions (Na+, K+, Ca2+)
and organic molecules (such as intermediate
metabolites, carbohydrates, lipids, proteins and RNAs).
Cell membrane
Organelles are described as membranous or Peroxisomes
nonmembranous.
Membranous organelles include:
Nonmembranous organelles include:
Plasma membrane
Microtubules
Rough-surfaced endoplasmic reticulum (rER)
Filaments (Actin filaments and intermediate
Smooth-surfaced endoplasmic reticulum (sER) filaments)
Golgi apparatus Centrioles
Endosomes Ribosomes
Lysosomes
Transport vesicles
Mitochondria
Plasma Membrane

Is a lipid bilayer structure visible with transmission electron microscopy.


Dynamic structure that actively participates in many physiologic and biochemical
activities essential to cell function and survival.

The total thickness is about 8 to 10 nm.

The plasma membrane is composed of an amphipathic lipid layer containing


embedded integral membrane proteins with peripheral membrane proteins attached
to its surfaces.
Plasma Membrane
Modified fluid-mosaic model
The membrane is a lipid
bilayer consisting primarily
of phospholipid, cholesterol
and protein molecules.

Amphipathic character:
The fatty acid chains of the
lipid molecules face each
other making the inner
potion of the membrane
hydrophobic and the
surface is hydrophilic.

Lipids are distributed


asymmetrically in the lipid
bilayer.
Plasma Membrane
Protein molecules constitute
approximately half of the total
membrane mass.

Most of the protein are embedded


within the lipid bilayer or pass
through the lipid bilayer completely.

Called Integral membrane proteins.


Or peripheral membrane proteins.
Plasma Membrane
On the extracellular surface of the
plasma membrane carbohydrates may
be attached to proteins.
Thereby forming glycoproteins
or to lipids of the bilayer, forming
glycolipids.
Constitute the surface of the cell
- cell coat or glycocalyx

Have specific functions in metabolism,


cell recognition, and cell association
and serve as receptor sites for
hormones.
Plasma Membrane

Microdomains of the plasma membrane, known as lipid rafts, control the movement
and distribution of proteins within the lipid bilayer.

Lipid rafts: is a localized regions within the plasma membrane contain high
concentrations of cholesterol and glycoesphingolipids
Is thicker and exhibits less fluidity than the surrounding.
And contain a variety of integral and peripheral membrane proteins involved in cell
signaling (Signaling platforms).
Plasma Membrane

Membranes typically split or cleave


along the hydrophobic plane to
expose two interior faces of the
membrane
E-face and P-face.
Integral membrane proteins have
important functions in cell
metabolism, regulation and
Integration.
Membrane proteins
Six broad categories of membrane proteins:
Pumps: Serve to transport certain ions (Na+)
actively across membranes. Also transport
metabolic precursors of macromolecules (amino
acids and sugar), either by themselves or linked
to the Na+ pump.

Channels: Allow the passage of small ions,


molecules and water across the plasma
membrane in either direction (passive diffusion).

Receptors: Allow recognition and localized biding


of ligands in process such as hormonal
stimulation, coated vesicle endocytosis and Enzymes: have a variety of role
antibody reaction. And structural proteins. proteins move within the lipid
bilayer of the membrane. Proteins can be localized or
Linkers: anchor the intracellular cytoskeleton to restricted to specialized regions of the plasma
the extracellular matrix. (Integrins).
membrane or act as transmembrane linkers between
intracellular and extracellular filaments.
Membrane transport and vesicular
transport
Simple diffusion: some substances (fat-soluble and small, uncharged molecules) cross the plasma
membrane by simple diffusion down their concentration gradient.
All other molecules require membrane transport protein.

Carrier Transfer small, water soluble molecules, they are highly selective.
Some carrier proteins such as the Na+/K+ pump or H+ pump,
require energy for active transport of molecules against their

proteins
concentration gradient.
Other carrier proteins such as glucose do not require energy and
participate in passive transport.

Channel Also transfer small, water soluble molecules, in general channels


are made of transmembrane protein with hydrophilic channels.

proteins
can be regulate by membrane potentials, neurotransmitters or
mechanical stress.
Membrane transport

Vesicular transport maintains the integrity of the plasma membrane and also
provides for the transfer of the molecules between different cellular compartments.

Some substance enter and leave cells by vesicular transport.

Forming the vesicle from the membrane or fusion of vesicles with the membrane.

Vesicular transport involving the cell membrane:


Endocytosis & exocytosis
Endocytosis
Uptake of fluid and macromolecules during
endocytosis depends on three different
mechanism.
Some of the endocytotic mechanism require
special proteins during vesicle formation
(Clathrin).
Pinocytosis (cell drinking) is the no specific
ingestion of fluid and small protein molecules via
small vesicle. Is performed by virtually every cell
in the organism. Is clathrin independent.
Membrane transport
Phagocytosis (Cell eating)
No selective process whereby occurs the ingestion
of large particles such a cell debris, bacteria and
other foreign materials.
The plasma membrane sends out pseudopodia to
engulf phagocytosed particles into phagosomes.
This mechanism is performed mainly by a
specialized group of cells belonging to the
mononuclear phagocytotic system.
Triggered by recognition of pathogen associated
molecular patterns (PAMPs)
leads to activation of nuclear factor kappa B (NF-
kB)
Clathrin independent, but actin dependent.
Membrane transport
Receptor mediated endocytosis allows entry
of the specific molecules into the cell.
Receptors for specific molecules called cargo
receptors, accumulate in the cell membrane
(lipid rafts).
Become a coated pits, that represents
aggregation of clathrin molecules on the
cytoplasmic surface.
Clathrin molecules then assemble and
change the shape of the plasma membrane
into a vesiclelike invagination.
Forms coated vesicle and is clathrin
dependent.
Exocytosis
Process by which a vesicle moves from the cytoplasm plasma membrane
Are two general pathways:

substances are continuously delivered in transport vesicles


Constitutive pathway to the plasma membrane.
(Immunoglobulins and procollagen)

Specialized cells (endocrine and exocrine cells and neurons) concentrate


secretory proteins and transiently storage them in secretory vesicles within
Regulate secretory the cytoplasm.
pathway A regulatory event (hormonal o neural stimulus) must be activated for secretion to occurs
The signaling stimulus causes a transient influx of Ca+ into the cytoplasm stimulates
secretory vesicles to fuse with the plasma membrane and discharge their contents.
Cytoskeleton
Microtubules

Are nonbranching and rigid They grown from the


hollow tubes of protein that microtubule-organizing
They create a system of
can rapidly disassemble in center located near the connections within the cell.
one location and nucleus and extend toward
reassemble in an other. the cell periphery.

Microtubules measure 20 to
Microtubules are elongated 25 nm in diameter
polymeric structures
The wall is 5 nm thick
composed of equal parts of
-tubulin and Btubulin Tubulin dimer have a
molecular weight 110 kDa.
Microtubules
The dimers polymerize in an end to
end fashion, head to tail with the
molecule of one dimer bound to
the molecule of the next dimer in
a repeating pattern.

Protofilament, longitudinal
contacts between dimers link them
into a linear structure.
Microtubules
Microtubules grown from
Polymerization of tubulin Each tubulin molecules
tubulin rings within the dimers requires GTP + binds GTP before it is
microtubule-organizing Mg2+ incorporated
center (MTOC)

Each microtubule
possesses a minus and at some point GTP is GTP-tubulin complex is
(nongrowing) end (- hydrolyzed to GDP then polymerized
tubulin)

The plus (growing) end


corresponds to -tubulin
and extends the cell
periphery
Microtubules

The speed of the polymerization or


depolymerization can also be modified by
interaction with specific microtubule-associated
proteins (MAPs).
Such as MAP-1, 2, 3 and 4, MAP-, and TOGp.
Regulate microtubule assembly and anchor the
microtubules to specific organelles.
The length of microtubules changes dynamically
as tubulin dimers are added or removed in a
process of dynamic instability.
Microtubules

Microtubules are involved in numerous essential cellular functions:

Intracellular vesicular transport


Movement of cilia and flagella
Attachment of chromosomes to the mitotic spindle and their movement during
mitosis and meiosis
Cell elongation and movement (migration) and
Maintenance of cell shape, particularly its asymmetry.
Microtubules

Movement of intracellular organelles is generated by


molecular motor proteins associated with
microtubules.
Two families of motor proteins:
Dyneins: move along the microtubules toward the
minus end of the tubule
Kinesins: move along the microtubules toward the
plus end.

Both are involving in mitosis and meiosis.


Dyneins move the chromosomes along the
microtubules and kinesins located between this
microtubules generate a sliding movement that
reduces the overlap.
Actin filaments
Are present in virtually all Actin also assemble
cell types spontaneously by
polymerization into a
Actin molecules (42 kDa) linear helical array.
Are abundant, of the filaments 6 to 8 nm in
protein. diameter

They are thinner, shorter G-actin= free actin


and more flexible than F-actin= polymerized
microtubules. actin
Actin filaments

which is hydrolyzed to The control and


The dynamic process of
ADP after each G-actin regulation of the
actin polymerization
molecule is polymerization process
requires the presence incorporated into the depends on the local
of K+, Mg2+ and ATP, filament concentration of G-actin

Which can prevent or


And the interaction of enhance
the actin-biding protein polymerization. Also are
(ABPs) responsible for the
filaments organization.
Actin filaments
Actin bundling Cross-link actin filaments into parallel arrays,
proteins creating actin filaments bundles.

Actin filament- Cut long actin filament into short fragments


severing proteins
Actin capping Block further addition of actin molecules by
proteins binding to the free end of an actin filament.

Actin cross-linking Are responsible for cross linking actin


proteins filaments with each other.

Actin motor Hydrolyzes ATP to provide the energy for


movement along the actin filament from the
proteins minus end to the plus end.
Actin filaments participate in variety of
cell functions
Anchorage and movement of membrane protein
Formation of the structural core of microvilli
May also help maintain the shape of the apical cell surface
Locomotion of cells
Is achieved by the force exerted by actin filaments by polymerization at the growing
ends.
Extension of cell processes
Many cells that exhibit small protrusions called filipodia, located around the
surface.
Intermediate Filaments
Diameter 8 to 10 nm
Intermediate filaments
Consist of subunits with
play a supporting or
general structural role. a molecular weight of
about 50 kDa.

Many of the stable


structural proteins in
with only minor genetic
intermediate filaments
evolved from highly modification.
conserved enzymes,
Intermediate Filaments
Intermediate filaments are formed from nonpolar and
highly variable intermediate filament subunits.
no posses enzymatic activity
Intermediate filament proteins are characterized by a
highly variable central rod-shaped domain with strictly
conserved globular domains at either end.

Intermediate filaments are assembled from a pair of


helical monomers that twist around each other to form
coiled-coil dimers.
to generate a staggered tetramer of two coiled- coil
dimers, each tetramer, acting as an individual unit ,
Intermediate Filaments
Intermediate filaments are a heterogeneous group of cytoskeletal elements found in various
cell types.
Intermediate filaments are organized into six major classes on the basis of genes structure,
protein composition, and cellular distribution.
Classes 1 and 2. These are the most diverse groups of intermediate filaments and are called
keratins (cytokeratins).
These classes contain more than 50 different isoforms
Keratins only assemble as heteropolymers; an acid cytokeratin and a basic cytokeratin
molecule form a heterodimer.
Intermediate Filaments

Each keratin pair is characteristic of a particular type of epithelium; however, some


epithelial cells may express more than one pair.

According to new nomenclature, keratins are divided into three expression groups:
keratins of simple epithelia
keratins of stratified epithelia
and structural keratins, also called hard keratins.
The latest are found in skin appendages such as hair and nails.
Intermediate Filaments
is the most abundant intermediate
Vimentin filament found in all mesoderm-
derived cells, including fibroblasts.

Class 3 Desmin is characteristic of muscle cells

Glial fibrillary acidic is found in glial cells (highly specific


protein (GFAP) for astrocytes)

is found in many peripheral nerve


Peripherin cells

with the exception of desmin, preferentially form homopolymeric filaments containing only one
type of intermediate protein.
Intermediate Filaments

Class 4. Historically this group has been called neurofilaments.


They contain intermediate filament proteins that are expressed mostly in axons of nerve
cells.

The three types of neurofilament proteins are of different molecular weights:


NF-L (a low-weight protein)
NF-M (a medium- weight protein)
NF-H (a high-weight protein).

Form heterodimer that contains one NF-L + one of the others. All three proteins form
neurofilamentsthat extend from the cell body into the ends of axons and dendrites.
Intermediate Filaments

Class 5. Lamins, specifically nuclear lamins, form a network-like structure that is associated with
the nuclear envelope.
Lamins are represented by two types of proteins, lamin A and lamin B.
are located within the nucleoplasm of almost all differentiated cells in the body

Class 6. This is a lens-specific group of intermediate filament, or beaded filaments


containing two proteins, phakinin and filensin.
The periodic beadlike surface appearance of these filaments is attributed to the globular structure
of the carboxy-terminus of the filensin molecule.

they function in chromatin organization, gene expression, nuclear architecture, and cell signaling
and provide an essential link between the nucleoskeleton and cytoskeleton of the cell.