BASICS OF CELLULAR STUDY

OUR
STA T G
STARTING
POINT

Whatt I’m going

Wh in to
t
assume you already
know!
 WHERE DO WE GO FROM
HERE?
• General principles of cell & tissue architecture
& development
• Non-typical and mechanistic approach
– Developing the “why” behind the “what”
– Correlate structures with function
– Overlaps with embryology & physiology
Thi will
• This ill be
b the
h most useful
f l course you take!
k !
“There is one universal priniciple of development for the most elementary parts of
organisms however they may differ: and that principle is the formation of cells.”

─ Theodor Schwann (1810-1882)

Microscopic Investigations (1839)

• THE ANIMAL IS THE

SUM OF ITS PARTS &
THEIR FUNCTIONS
– Cells, tissues & organs are
specialized
– All animals start as single
cells and undergo changes
to achieve final form
– Morphogenesis & growth
are common to cells,
tissues & organs
THE FIRST KEY DEFINITION

• CELL: A mass of protoplasm

surrounded by a membrane and
containing a nucleus and organelles
– The fundamental unit of life
– CELLS DO NOT EXIST AS
INDEPENDENT ENTITIES
(No, not even in blood…as we’ll see later!)
 THE SECOND KEY
DEFINITION

• TISSUE: An aggregation of cells and

intercellular materials specialized
p for
specific functions
– Cells are always
y p part of a tissue
– Tissue’s function determines what cells are
p
present
– Cells make tissue function possible
– Structure of cells often p
predictable based on
tissue function & vice versa
FOUR “BASIC
TISSUES”
• EPITHELIUM
• CONNECTIVE
TISSUE
• MUSCLE
• NERVOUS TISSUE
– Organs
g made up p of
these
– At least 2 basic tissues
in any organ
in
 THE THIRD KEY DEFINITION
ORGANS:

• Aggregations of cells,
tissues, and intercellular
materials specialized for
specific functions

– Tissues are not autonomous

– Always integrated with other
g
tissues to form organs

• Separation of tasks and of

cells & tissues is a
hallmark of organs
The animal…is to be viewed as a complex organism made up of an assemblage of simple microscopic
organisms, the cells…Each…makes its own highly specific contribution to life…Similar kinds of cells
doing a similar job tend to be grouped together within the tissues…A single…organ carries out multiple
functions because it has multiple tissues and multiple kinds of cells in it.
it

─Sherwin B Nuland, MD
Doctors: A Biography of Medicine (1988)
 Limits
ts on
o Cellular
Ce u a Growth
G owt
• Must have enough
cytoplasm to function
• Can’t have too much
for diffusion, etc.
– Some structural
“leeway”
leeway in size
– Ability to compensate
isn’t infinite

A Single Cell!
SIZE RANGE IN ANIMAL CELLS

• Smallest: 3-4 μm
– Some cells of blood,
e g quiescent
e.g.
lymphocytes
• Largest:
g 100-150 μ
μm
– Some neurons
– Monocytes
– Skeletal muscle
 SMALL CELLS HAVE
LIMITATIONS

• Typically very little cytoplasm

– Limits functions
– May have inactive inclusions
– Nuclear material condensed
– M be
May b “transformed”
“ f d” to an active
i state
LARGE CELLS HAVE
LIMITATIONS

• Greater size limits

internal diffusion rate
of materials
• Have compensatory
mechanisms
– Compensation isn’t
unlimited
 CELL DEATH
• Many cells are pre-programmed
to die
– Major mechanism of morphogenesis
– Shapes and sculpts limbs, etc.
– Timing is exact and preprogrammed
• Many embryonic structures only
temporary
– Removes the
h “scaffold”
ff ld ffrom the
h
“building”
• Examples:
– Formation of paws
– Wound healing
 Differentiation:
How We Get From….

Here to Here
 Differentiation
• Process by which cells come to have
p
different characteristics & capabilities
• Differentiated cells produce different
proteins than its p
p progenitors
g
– Not all capabilities expressed
• Not limited in time
– Can continue throughout life, e.g., wound
healing & hemopoiesis
• Usually a precursor or “stem” cell type is
involved
– Stem cells often present in tissues/organs
 Stem Cells
• A general term
• A pop
population
lation of
“reserve” cells
– Quiescent
– Can be stimulated
– Undergo g
differentiation
– One stem may
produce
d severall
cell lines
STRUCTURAL
S UC U ADAPTATIONS
ONS

• Remember: Anatomy = Physiology!

• Applies at all levels
– Cells
– Tissues
– Organs
g
– Whole animal
• A camel is a camel because he has to be
a camel to survive in a camel’s world!
 CELLULAR STRUCTURE IS AN
ENGINEERING PROBLEM!
• If it isn’t
designed
right it won’t
work right!
• Applies
A li at all ll
levels of
structural
study

The Tacoma Narrows Bridge Collapse, 1940

 PLASMA MEMBRANE
• Defines cell’s limits
• Controls passage of
materials
• Site of receptors,
markers, etc.
• Can be inferred but not
demonstrated with LM
• Stereotypical
appearance in EM
“FLUID MOSAIC” MODEL

Singer & Nicholson, 1972

PLASMA MEMBRANE
 PM ADAPTATIONS FOR
ABSORPTION/SECRETION
• Process involves transfer
across plasma membrane
• Must optimize transfer based
on:
– Flow rate
– Length and diameter of tubule
• May be quite limited
– Degree
g Of permissible
p variation
– Rate of transfer per unit of area
– “Best case” and “worst case”
– “Safety Factor”
• Assumptions: rate is
predictable, stable, and
limited
– Examples:
E l kid
kidney tubules,
b l
intestinal cells, epididymal cells
MICROVILLI

• LM seen as
“brush border”
– Individually not
resolvable
– Uniform length &
height
– Intestine, kidney,
some other sites
 MICROVILLI

• Filled with cytoplasm, surrounded with PM

• Mayy contain actin filaments
• May be arranged for maximum # per unit area
• Fairly small structures
 PM ADAPTATION FOR
ABSORPTION/SECRETION
• BASAL FOLDS
• “Reverse” of
microvilli
– Basal end of cell,
not apex
– Infolds of PM
containing
y p
cytoplasm
• Often contain
mitochondria
• Associated with
active transport
– Slower transfer
rate
– Transporting
“finished goods”
ADAPTATIONS FOR MOVEMENT
• Cell migration
• Movement of materials on
cell surface
• Always involves
microtubules
– Cilia and flagellae
g
– Amoeboid motion
• Entire cell or only parts of it
mayy be affected
• Directional
• Energy from ATP
• Interact with aqueous
environment
– Respiratory, reproductive
systems
• An ancient development
– The only solution!
CILIA & FLAGELLAE
STRUCTURE OF CILIA
 Don’t Confuse Cilia & Microvilli!
• An order of
magnitude
g
difference in size
• Cilia can be 10-
100 μm long, and
at least 10 μm
thick
• Microvilli rarely
exceedd 11.00 μm
thick and 10 μm
long
 ADAPTATIONS FOR
MAINTAINING SHAPE
• Odd shapes crucial to
function
– Internal “scaffolding”
scaffolding
– May serve other needs
• Internal routing of
materials
• “Wiring” for
information transfer
• Disruption causes
problems
– Chemotherapy agents
• e.g. Colchicine
 MICROTUBULES & MICROFILAMENTS

• Vital to movement
normal architecture
• Ubiquitous and variable
in makeup
– May be contractile
• Cilia, flagellae, and
amoeboid movement
– May be “stiff”
– May be for internal
transport
– Polymeric structures
• Shorten & lengthen
g byy
adding dimers
• Principal component is
tubulin
• May contain ATPase,
dynein
 MICROTUBULES
• 20-50 nm (200-500 Å)
• Cytoskeleton
– Mitotic spindle, cilia, flagella
 CYTOSKELETAL MICROTUBULES
• Maintenance of shape of odd cells, e.g. neurons
 MICROFILAMENTS
• Intermediate • Thin microfilaments
filaments – Mainly actin for
intracell lar
intracellular
– Internal structural
contractility
“scaffold” • Amoeboid motion,
– Anchor nucleus division etc
division, etc.
– Connect cytoskeleton – Myosin usually
to PM involved as well
– Maintain shape of – Gel-like network in
cytosol of other thin
nuclear envelope filaments
 MICROFILAMENTS & INTERMEDIATE
FILAMENTS
• Smaller than
microtubules (6-10
nm) & associated
with contractility
– Actin & myosin
• May be involved
with adhesion
structures
– Tonofilaments of
desmosomes
• Also a cytoskeletal
element
• Variable in size,
related to function
MICROFILAMENTS

Astroglial fibers in an astrocyte

 MICROFILAMENTS

• Microfilaments
Mi r fil nt & secretory
r t r vesicles,
i l rat
r t ovarian
ri n
granulosa cells
MICROFILAMENTS

Actin & myosin in skeletal muscle

 ADAPTATION FOR SURFACE PROTECTION
• Cells are susceptible
p
to damage
– May be
unavoidable, e.g.
Intestinal cells
eroded by digestive
juices
– Strategy is to delay
it
• Glycocalyx
– Expendable &
renewable surface
covering
– Resistant to erosion
– Can be “sacrificed”
 GLYCOCALYX
• Cell surface coat
– Carbohydrate in nature
• Glyco = “sweet”
sweet calyx =
“husk”
– Term coined by John Luft in
1965
• F
Foundd on all
ll cells
ll to some
extent
• Usually heaviest at free
surface
• Not quite “basement
membrane”
• Functions usually p protective
otective
• Some enzymatic activity
• PAS+ / RR+ in EM
• May not be obvious in routine
preps
 GLYCOCALYX

• LM image courtesy of Dr. Ihab El-Zhogby

 ADAPTATIONS FOR TISSUE
INTEGRITY & FUNCTIONAL
COHESION
• Tissues are INTEGRATED both
structurally & functionally
• Cells are not independent
p units
• Cells must communicate
• Cells must maintain contact with each
other
• A whole
h l series
i off PM specializations
i li i
Occluding (“Tight”) Junctions
• Adjacent PM’s are fused together
OCCLUDING JUNCTION
• Function to
separate “inside”
“i id ”
from “outside”
• Control
C t l passage off
materials; forces
them to go
through a cell
• Used to control
osmotic pressure,
ion flux, etc.
 DESMOSOMES
• Most common
membrane
specialization
p
• Found in all types of
tissues & organs
• Similar
Si il tto adhering
dh i
junction
– Also for mechanical
int it
integrity
– Distinguished by dense
filamentous component
– Anchor cells to each
other
• A “spot weld” versus a
bead weld”
“bead weld
 SPECIALIZATIONS FOR
COMMUNICATION
• Cells have to know what’s going on
around them
• Tissue function depends on this
– Smooth muscle
– Cardiac muscle
– Glandular epithelium
– Many other examples
 Gap Junction
• Limited area of plasma
membrane
• Found in all tissues
• Not for adhesion but for
communication
• Site of lowered or
variable resistance to
passage of ions
• Membrane gap is 20Å or
so
• “Pores” on either side
• Cell-to-cell
C ll t ll
communication
Gap Junctions
 NUCLEUS & NUCLEAR ENVELOPE
• “Command & Control”
center of cell
• All eukaryotic cells have
the entire “blueprint”
– MOST of it isn’t used
– Degree of specialization
affects how much is
accessible
– Physiological state
determines appearance
• Broken down &
reconstructed each cycle
• Nuclear
N l r morphology
rph l
varies with function &
state
• Envelope continuous
with RER
 NUCLEUS
& RER
• Nuclear envelope
& RER are
continuous
– Ribosomes found
on NE outer
t
surface
• Nuclear pores
p
located at
turnbacks of the
NE
NUCLEAR PORES
• Openings in
nuclear
envelope
• Allow
passage
p g of
RNA
• Complex
structure to
control
movement
NUCLEAR PORES
 SYNTHESIS & SECRETION
• MOST cells have
some synthetic
capability
• SOME cells are
p
specialized for it
• ALL use the same
structures to do it
– Endoplasmic
reticulum
– Golgi apparatus
ENDOPLASMIC RETICULUM

• Two types:
– Rough
g ER functions for protein
p synthesis
y
• Described many times from LM studies
• EM reveals true nature
• Porter coined term in 1950’s
– Smooth ER functions in various ways
• Lipid synthesis
• Enzymatic degradation pathways
• Special role in muscle
 RIBOSOME
• Functional unit
of RER
• Bound & free
types exist
– Identical
structure
– Large
L & small
ll
subunits
– Entire ribosome
complex about
300Å
ROUGH E.R.
• Prominent feature
in secretory cells
– Pancreatic cells
– Plasma cells
– Peptic cells
• Amounts vary with
cell function
• Usually some
present, may be
minor amount
• Accounts for LM
visible
BASOPHILIA
BASOPHILIA & THE RER
 GOLGI APPARATUS
• Known since 19th
Centuryy
– Visible in LM
– Nature & existence
d b t d until
debated til 1960’s
1960’
• Functions to modify
& package products
of RER for release

• Camillo Golgi (1843-1926)

GOLGI APPARATUS
 GOLGI APPARATUS

• Contains enzymes for attaching

y
carbohydrate & lipid
p moieties to peptides
p p
SMOOTH ENDOPLASMIC RETICULUM
• Visible only in EM
• Prominent in cells
making steroids or lipids
– Leydig cells
– Luteal cells
• Role
R l iin d
detoxification
t ifi ti
– Large amounts in
hepatocytes
• C
Collection
ll i off
interconnected tubules &
vesicles
• Membranous but not
“studded” with
ribosomes
Anatomy and physiology form but the vestibule of medical education. They
teach the normal structure of the body, the normal function of the parts,
fluids, organs, and the conditions under which they operate.
— Abraham Flexner (1866-1959)
Medical Education in the United States and Canada (1910)