BIOLOGY 205: CELL BIOLOGY — FALL 2016

 
Lectures: Tuesday and Thursday, 10:30-11:50 am
Leidy Labs Room 10
 
Lecturers: Dr. Wei Guo (304E Lynch Laboratory, guowei@sas.upenn.edu)
Office hour: Thursdays 2:30 – 3:30 pm
Dr. Tatyana Svitkina (304K Lynch Laboratory, svitkina@sas.upenn.edu)
Office hour: Fridays 4:00 – 5:00 pm

TAs: Ruby O’Lexy – Email: cortesr@sas.upenn.edu

Maribeth Harlan – Email: mharlan@sas.upenn.edu
 
 
Recitation section I Tuesdays 5:00 – 6:00 pm (10 Leidy Lab)
Recitation section II Wednesdays 5:00 – 6:00 pm (10 Leidy Lab)
 
Textbooks:
Molecular Biology of the Cell, 6th edition (Garland Science) by Alberts, Johnson,
Lewis, Raff, Roberts & Walter. Note: 5th edition is acceptable.
The Cell: A Problem Approach, 6th Edition (Garland Science) by Wilson and Hunt.
Note: 5th edition is acceptable.

Exams:  Three midterms will be administered during regular class periods. Each of
these exams will be worth 100 points. After normalizing to a common mean
the low score will be dropped. There will be no make-up exams. The final
exam is worth 200 points.
 Ernst Haeckel “Kunstformen
der Natur” (1904)

CELLS

Bacteria

Animals:
Multicellular organisms

Ciliata:
Sophisticated
cells

Animal cells
Plasma membrane important for life, creates compartment in which
all biochemical reaction and all sophisticated biological molecules
exists. First function is to make a compartment for biochemical
reactions. Also provide means for communication between
biochemical reactions inside the cell and the external world. Internal
organization of the cell: plasma membrane separates interior
from exterior, also organizes biochemical reactions to make them
more efficient;

Multicellular organisms provide another level of organization

Have cells dedicated to specific functions. Multicellularity also
applies additional challenges: how to communicate (mediated
by plasma membrane activity), another challenge is that cellular
strategy for survival is different (individual cells must learn to
Coordinate activity at whole organism level, if perpetual survival
can lead
To cancer)
 CELLULAR ORGANELLES

Centriole:
Lysosome: Nucleus:
Assembly of
Degradation of DNA storage
mitotic spindle,
macromolecules Transcription
cilia and flagella
Ribosome assembly

Vesicles:
Endocytosis,
ER:
exocytosis,
Synthesis
intracellular
of proteins
traffic
and lipids;
calcium
Mitochondria: storage
ATP production;
apoptosis
regulation Golgi:
Post-
translational
modifications
Animal cells

Cytoskeleton:
Cell motility
ER- sophisticated network of membrane structures
Store Ca2+ that are important signaling molecules.

Golgi- takes newly synthesized proteins from ER.

Makes modifications, mostly adding saccharides

Cytoskeleton- mediates all forms of cell motility

Vesicles: serve as packages

Endocytosis- take materials from outside
Exocytosis- release material into cell exterior
Intracellular Trafficking- move materials within the cell

Centrioles:
Assembles mitotic spindle, important for cell division
Assembles cilia and flagella, important motile and sensory organelles

Lysosome: compartment that functions like recycling bin.

Subunits of proteins, nucleic acids, and lipids are released
Into the cytoplasm to be reused for synthesis machinery.
 ELECTRON MICROSCOPY OF PLASMA MEMBRANE

Electron microscopy allowed scientists to visualize membrane.

Shows three-layered structure: two black layers and a white layer
 PHASE SEPARATION Water molecules prefer to interact wi
Intrinsic property than with hydrophobic molecules. Fo
of separation between around the hydrophobic molecule (en
hydrophobic and unfavorable). water molecules would
hydrophilic hydrophobic molecules, leading to se
phase.
Polar molecules
will react with
charges on water
Hydrophilic molecules Hydrophobic molecules
micelles.
Hydrophobic tails
interact with dirt and AMPHIPATHIC MOLECULES
polar groups with - Combine hydrophilic and hydrophobic molecule
water. Detach the
dirt

If find boundary
between water and If put on body of water, form
air, put polar heads micelles where hydrophobic tails
on water and fatty will be buried in middle of
chains in air- most spherical particle and polar grou
energetically will face water.
favorable

Micelles not u
biochemical r
Fatty (palmitic) acid
Because enz
in water
 MICELLES AND BILAYERS

Single fatty
acid chain

Two fatty acid

chain
 LIPOSOMES

Hydrophobic
portions are still
exposed to water

Creates compartment with water

That can allow enzymes to function
 IS MEMBRANE REALLY A BILAYER?
Experiment by Gorter and Grendel, 1925
Gorter and Grendel’s model of membrane structure

Used red blood cells because have only one

membrane: plasma membrane. Do not have
internal membrane organelles. Allows them to
measure area plasma membrane. Took a
sample and counted number of cells and
measured dimensions. Multiplied by total
number of cells. Then they took equivalent
sample, extracted lipids and floated in a bath of
water. Amphipathic molecules stick tails in air
and heads in water. Moved slider to find
position where all lipid molecules form a
monolayer. Afterwards, measure area and
compared with measured plasma surface area.
The area was twice plasma surface area.

2 Problems: didn’t take into account biconcave Langmuir’s trough to measure area of the lipid monolayer

shape of cells so total surface area greater;

 Backbone is glycerol. Third
PHOSPHATIDYLCHOLINE carbon usually forms ester wit
phosphate. Phosphate linked t
polar group which in this case
choline but it can vary.
Consists of polar group and two hydrophobic tails
-> one of the tails is fully saturated chain with single bonds between individual
carbons. Makes it straight.
->other tail has at least one double bond with cis configuration that creates kink
in the fatty acid chain. Kink important in expanding size of chain. Can have up to four
double bonds. Corresponds to size of polar group: the bigger the polar group the
more double bonds you need to create kinks to expand size of the chain

Plasma membrane is a fluid that can freeze. If membrane is completely saturated

throughout, would freeze even at body temperature. However, with kink tails, would
be able to withstand colder temperatures. Artic fish have lipids with multiples double
bonds/kinks to prevent membrane from freezing.

Length of fatty acid chain is variable but not hugely: between 18 and 22 carbon
atoms
PHASE TRANSITION
which has a net negative charge
Sphingomyelin not based off of
rom carboxyl group on serine. It is
PHOSPHOLIPIDS glycerol back bone
estricted to inner leaflet of plasma
but on sphingosine backbone.
membrane, making the inner
eaflet negatively charged.
Based on sphingosine GLYCOLIPIDS Some of the saccharides are
backbone, negatively charged.
Major difference from Restricted to outer leaflet of
other lipids is plasma membrane.
Absences of phosphate- May provide negative charge
not phospholipids, to outside- important for cell
sphingolipids to cell
interaction/communication.
 PHOSPHATIDYLINOSITOLS
Phosphatidylinositol Phosphatidylinositol phosphates
PHOSPHATIDYLINOSITOLS- are important signaling lipid that is present
In the cell in very minor amounts. Important role in coordinating intracellular activties.

Have traditional glycerol backbone with two fatty acid chains and a phosphate attachme
To head group.

As a head group, have a sugar, inositol, which is a 6 carbon monosaccharide.

Pretty big polar group, so most PHOSPHATIDYLINOSITOLS have four double bonds
on their chain
Can be phosphorylated on positions of carbon 3,4,5 in a combinatorial manner.
Different phosphorylation create PHOSPHATIDYLINOSITOLS with different
signaling functions.
 MEMBRANE BILAYER ASYMMETRY

Phosphatidylcholine
Sphingomyelin

Phosphatidylethanolamine Phosphatidylserine

Strict: Glycolipids are always on outside and phosphatidylserines are always on inside.
If phosphatidylserine is on outside of cell, signal to immune system to kill the cell.
 CHOLESTEROL

Ring structure very sturdy and inflexible. short hydrocarbon

tail. Very small polar head in form of hydroxyl group. Rigid short molecule,
Fits close to outside surfaces of bilayer. Incorporation makes lipid bilayer stronger
, more stiff, and less permeable to different solutes but still permits flexibility and fluidity
PHOSPHOLIPID – CHOLESTEROL INTERACTION
MEMBRANE FLUIDITY
MEMBRANE PERMEABILITY

Membrane are fluid because lipids

are able to undergo lateral
diffusion, rotate, flex their tails.
Difficult to flip-flop, performed by
special enzymes, which make the
asymmetric distribution of lipids in
membrane. Spontaneously, it
rarely occurs
MEMBRANE PERMEABILITY

Easily move across membrane,

Includes gases, steroid hormones

Small fraction of them can

cross membrane based on
thermal fluctuations

Probability to cross even smaller

Cannot cross membrane at all

 LIPID RAFTS IN ARTIFICIAL LIPOSOMES

Atomic force
microscopy

Phosphatidylcholine
+ sphingomyelin

Phosphatidylcholine
+ sphingomyelin +
cholesterol
PLASMA MEMBRANE STRUCTURE

SM –
sphingo-
myelin

GS – glyco-
sphingolipid

PC –
phosphatidyl-
choline

PE –
phosphatidyl-
ethanolamine

PS –
phosphatidyl-
serine
Can experimentally create lipid rafts in liposomes by adding
Sphingomyelin to cholesterols. Cholesterol preferentially interacts
With Spingomyelin, and this causes their tails to straighten up and
Cluster up together because have energetic preference to interact
with each other. Causes domains to be a little thicker, straightening
Of hydrophobic tails.

Iipid rafts are controversial- sometimes found and sometimes not.

Size not determined. Possibly a signaling platform, signaling
Proteins prefer to co-cluster with cholesterold and sphingolipids
And thicker membranes

Rafts are probably very dynamic: difficult to detect and characterize

 CELL MEMBRANES
1. Membranes are designed to enclose and compartmentalize a cell

2. Membranes are made of amphipathic molecules:

- Phospholipids
- Cholesterol
- Glycolipids
- Phosphoinositides

3. Membranes properties:
- membranes are asymmetric
- membrane is fluid
- fluidity can be controlled by lipid composition

4. Functions of membrane lipids:

- structural
- accommodation of proteins
- signaling
- communication with environment