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Objectives
• General
Get general idea of cell organization.
Understand what changes in organelles tell you about dynamics of cells.
Develop global perspective on cell function
• Specific (as in the learning objectives)
I.Introduction
II. Plasma membranes
III. Organelles
IV. Cytoskeleton
V. Inclusions
Introduction
• Subunits if Life:
• Cells are the structural units of all living organisms.
• There are two fundamentally different types of cells
– Prokaryotes
– Eukaryotes
Prokaryotic cells
• Simplest organisms; single cell organisms (bacteria)
– Cytoplasm is surrounded by plasma membrane and encased in a rigid cell wall.
• single circular molecule of DNA
• No distinct interior compartments
• No histones (specific proteins bound to DNA)
• No membranous organelles
Eukaryotic cells
• Characterized by compartmentalization by an endomembrane system, and the
presence of membrane-bound organelles.
– Distinct nucleus and envelope
– Chromosomes - DNA associated with protein
– Numerous membranous organelles
– Cytoskeleton (internal protein scaffolding)
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Importance of Studying Cell Structure:
• Changes in cell structure provide:
– important clues about changes in cell function.
– important clues about pathologic changes.
• In pathologic conditions cells exhibit either too much or not enough of a normal
function
Changes in structure can indicate a great deal about what functional changes are
occurring
Liver
Cell Components
• Cytoplasm
– a matrix, or cytosol, in which are embedded the organelles, the cytoskeleton, and
deposits of carbohydrates, lipids, and pigments.
– Plasma membrane encloses the cell- phospholipid bilayer
• The Nucleus
– Houses the genetic material (DNA)
Plasma Membrane
Plasma Membrane: Molecular Composition
Phospholipid Bilayer
– Each phospholipids has a polar head located at surface of membrane(hydrophilic)
– Nonpolar tail of 2 long fatty acid chains (hydrophobic)
– Phospholipids (eg, lecithin, phosphotidylserine, phosphotydylcholine,
phosphotidylethanolamine, sphingomyelin) are by far the most abundant.
Cholesterol is also a constituent of the membrane and determines the fluidity and help
improve the rigidity.
Proteins
• 50% of membrane weight
• 2 groups
• Integral proteins- span the entire lipid bilayer
• Some trans membrane proteins may serve as hydrophilic channels for the passage
of water and water-soluble materials
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Proteins
• Peripheral proteins- looser connection, usually cytoplasmic, often associated
with 2° messenger system or cytoskeletal apparatus
Glycocalyx
• Carbohydrate chains that are covalently linked to integral proteins or
phospholipids
• Composition varies from cell to cell
• Form fuzzy coat on surface of cell
– Added measure of protection to cells
– Bind to substances outside of cell (adhesion)
– Cell recognition
Membrane Structure
Fluid mosaic model of membrane structure
• Fluid mosaic model describes biologic membranes as "protein icebergs in a lipid
sea."
• The mosaic disposition of membrane proteins, in conjunction with the fluid nature
of the lipid bilayer, constitutes the basis of the fluid mosaic model for membrane
structure
• The model is not static.
• Integral proteins exhibit lateral mobility in the bilayer and may undergo
rearrangement determined by their association with peripheral proteins.
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– Facilitated diffusion
– Active transport
Signal Reception
• Many cells form communicating junctions that couple adjacent cells, allowing the
exchange of ions and small molecules
• Through these channels, also called gap junctions, signals pass directly from cell
to cell without reaching the extracellular fluid
• In other cases, cells display membrane-bound signaling molecules that influence
other cells in direct physical contact
Endocytosis
• Cells engulf extracellular substances and bring them into the cytoplasm in
membrane-limited vesicles by mechanisms described collectively as endocytosis.
• Obtain raw materials for cell functions
• Defend organism from noxious chemicals and harmful biologicals
• Phagocytosis
• Macropinocytosis
• Pinocytosis
• Can involve specific receptors on surface or can be passive
• Receptors concentrate uptake
• In all cases some extracellular material internalized passively
Endocytosis
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• In phagocytosis ("cell eating"), the cell engulfs insoluble substances, such as
large macromolecules or entire bacteria. The vesicles formed are termed phagosomes,
• Can involve specific receptors on surface or can be passive
• In all cases some extracellular material internalized passively
• Plasma membrane invaginates to form pit
• Opening of pit constricts to form narrow neck
• Apposing membranes fuse to seal pit into vesicle
• In pinocytosis ("cell drinking"), the cell engulfs small amounts of fluid, which
may contain a variety of solutes.
• Pinocytotic vesicles are usually smaller than phagosomes.
• The pinch off from cell surface and most eventually fuse with lysosomes
Exocytosis
• Exocytosis removes substances from the cell.
• Cells use this process both for secretion and for excretion of undigested material.
• A membrane-limited vesicle or secretory granule fuses with the plasma membrane
and releases its contents into the extracellular space, without disrupting the plasma
membrane. (Membrane trafficking).
Organelles
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Membrane Limited Organelles
Mitochondria
• Membranous bag of proteins involved in aerobic energy production and storage
• Regulate ion content of cytoplasm.
• Store factors important in regulated cell death (apoptosis)
• Vary in size, shape and number
• 0.5 - 1 micrometer in diameter & up to 10 micrometers long
• Move freely within cytosol and tend to aggregate in areas with high energy
demands
• Visible by light Microscopy
• Outer membrane:
– permeable
– contains porin, a transmembrane pore-forming protein which allows free passage
of small molecules
– contains enzymes that convert lipids into forms that can be metabolized by
mitochondria
• Inner membrane:
– separated from outer by “intermembranous space:
– thinner and thrown into folds -- cristae
– highly selective permeability via elementary particles that generates proton
gradient that produces heat and generates ATP via oxidative phosphorylation (aerobic
respiration)
• Inner Matrix:
– rich in proteins and nucleic acids
– Contains enzymes for Krebs cycle, fatty acid beta oxidation and protein
synthesis, mitochondrial DNA, RNA and ribosomes
– contains dense granules which are the storage site for divalent cations
– contains one or more strands of double stranded circular DNA
• Cells with higher energy demands have more mitochondria and more cristae per
mitochondria
Ribosomes
• Small particles composed of ribosomal RNA and protein
– RNA imparts an intense basophilia to the cytoplasm
• Composition and appearance: beads on a string at the EM level,
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• Beads have a large and small subunit that don’t combine until protein synthesis
begins
• Cytoplasmic basophilia in LM is clue of extensive rER
• Seen as basophilic bodies, Nissl substance in neurons, ergastoplasm in glandular
cells
• Function:
• protein synthesis in either the cytosol (when as free polyribosomes) or as bound
polyribosomes on the endoplasmic reticulum (rough ER)
• -free polyribosomes synthesize intracellular proteins
• -bound (rER) polyribosomes synthesize proteins destined for the extracellular
space or within the membrane - they see extracellular space
Ribosomes & Protein Synthesis
Endoplasmic Reticulum
• Membrane bounded element containing enzymes, receptors, and transporters
• Appears as elongated, flattened, rounded or tubular vesicles that have either a
rough (rER) or smooth (sER) surface with gradations between the two (smooth and rough
ER can share the same lumen)
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• SER functions in :
• Steroid synthesis
• Neutralization of poison
• Lipid metabolism
• Phospholipid synthesis
• Glycogen utilization
Golgi Apparatus
• smooth, membrane delimited organelle containing various enzymes
• By EM, stacks of flattened membranes that are closely associated with vesicles .
• 3 components:
– slightly curved flattened stacks (3 - 10) of cisternae
– cisternae nearest to rER is called the forming, convex, or cis face.
– On the opposite side of the Golgi complex, is the maturing, concave, or trans
face,
• several small vesicles near on cis face are transport vesicles
• fewer larger vesicles near the trans face are the condensing vesicles
Lysosomes
• Lysosomes - membrane-bound vesicles containing a large variety of hydrolytic
enzymes; mostly hydrolases.
• Are a product of the Golgi and fuses with late endosomes to facilitate degradation
of endosome contents
• Are usually spherical, range in diameter from 0.05 to 0.5 micrometer
• In EM present a uniformly granular, electron-dense appearance
• Lysosomes are intracytoplasmic acidic vesicles involved in degradation of
numerous substances
• Lysosomes are particularly abundant in cells exhibiting phagocytic activity
– macrophages,
– neutrophilic leukocytes).
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• Lysosomal enzymes have optimal activity at an acidic pH.
Stages of Lysosomes
• Primary lysosomes have not entered into a digestive event .
• When primary lysosomes fuse with the membrane of the phagosome and empty
their hydrolytic enzymes into the vacuole, the composite structure is now termed a
secondary lysosome.
• After digestion of the contents of the secondary lysosome , indigestible
compounds are retained within the vacuoles, which are now called residual bodies
• When primary lysosomes fuse with an organelle or cell component, the resuling
structure is called autophagosome.
Peroxisomes (Microbodies)
• Small, membrane-limited enzyme-containing vesicles spherical bodies
– 0.5 to 1.0 um in diameter somewhat larger than primary lysosomes
– contain oxidative enzymes -- catalase
• Involved in the formation and breakdown of intracellular hydrogen peroxide
– used for killing phagocytosed bacteria
• Involved in beta oxidation of fatty acids
• Content is moderately electron-dense
.
Secretory Vesicles, or Granules
• Secretory vesicles are membrane structures found in those cells that store a
product until its release
• They contain a concentrated form of the secretory product .
• Secretory vesicles containing digestive enzymes are referred to as zymogen
granules.
Non-membrane Limited Organelles
Cytoskeleton
• Intracellular Movement
– Contraction can move cytoplasm
– Attach to other organelles and with molecular motors coordinate their movement
• Outside-In signalling
– Bind to integral membrane proteins and transduce signals from outside
environment
The Cytoskeleton
• Network of protein fibers that provide:
• Support to cell shape and anchoring organelles
• Support to transport molecules/vesicles within the cell.
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• Intercellular connections linking cells together and attaches to substrate (non-
cellular linkage) linking cell to substrate
• Can be very dynamic
Microfilaments
• Types
– Thick (13-16 nm diameter) Filaments- Myosin
– Thin (6-8 nm diameter) Filaments- Actin
• Major protein of muscle cells where they are critical component of contraction
apparatus
• Actin (and probably myosin) found in almost all cell types
Actin Microfilaments
• 2 strings of bead-like subunits twisted together in a rope
– globular subunits are stabilized by Ca++ and ATP
– form stable subunits with myosin
Microvilli
• cyclindrical, membrane-bound cytoplasmic projections
• core of 25-30 actin microfilaments crosslinked by villin anchored into terminal
web
– complex of actin and spectrin molecules
Stereocilia
• Long microvilli
• Found only in:
– epididymis
– sensory hair cells of cochlea -- signal generation
• non-motile, rigid structures
• core made of actin filaments
Intermediate Filaments
• Reasonably stable elements serving primarily structural function
• Bind other cytoskeletal and intracellular structures to one another
Microtubules
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• Elongated macromolecules made up of globular protein subunits (hollow
cylinder)
– Composed of heterodimer of alpha tubulin and beta tubulin subunits in helix that
polymerizes into a microtubule
• Polymerization directed by microtuble organizing centers:
– Cilia
– Basal bodies
– Centrosome
• Polymerization can be highly dynamic (mitotic spindle) or can be relatively stable
(cilia)
• Change in length accomplished by fast growth at one end (+) while other end
grows slowly (-) or disassembly at negative end.
• Change in length controlled by environment and MAPs. ( microtubule-associated
proteins)
Microtubule Functions
• Cell shape maintenance and intracellular movement (microtubles are stiff)
• Maintenance of cell polarity
• Chromosome movement during division
• Beating of cilia and flagella
• Track for microtubule-based motor proteins that distribute vesicles throughout the
cell
Centrioles
• Small cylindrical paired structures located in centrosome
• Made of nine sets of microtubule triplets arranged in a circle and linked laterally
forming a centriole
• Each triplet consists of 1 complete and 2 incomplete microtubules fused
• Two centrioles (at 90 degrees) are found near the nucleus of interphase
• In dividing cells, the centrioles duplicate during the S period, migrate to the
opposite poles of the cell and form the organizing centers for the mitotic spindles
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• Short, fine, hair-like, beating structures
• Associated with basal bodies
– thin, dark-staining band at base of cilia
– Similar to centriole
– result of centriole replication
Cilia
• Contain an organized core of microtubules
– 9 + 2 arrangement
– Contains a pair of dynein arms which make a temporary bridge with the B
microtubule of adjacent doublet
• Abundant in respiratory epithelium, intestine, urogenital tracts
• Beating of cilia moves fluid along surface of sheets of cells
• Abnormal Cilia may be found in chronic respiratory problems
Inclusions
Glycogen
• Carbohydrates are stored as glycogen granules
– By LM, stain acidophilic (associated protein) or by carbohydrate stains (PAS)
– by EM, appear as electron-dense particles
Lipids
• Lipids (another storage form for energy)
– stored primarily by adipocytes
– ability to accumulate in other cells
• hepatocytes
– exist as free cytoplasmic droplets
• Pigments
– exogenous such as carotene or dust
– endogenous: produced by the cells
• hemoglobin
• melanin
• lipofuscin -- wear and tear end product
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