• Individual cells that form our bodies can grow, reproduce, process information, respond to stimuli, and carry out an amazing array of chemical reactions, these abilities define life

• Humans and other multicellular organisms have tons of cells that are organized into complex structures, but many consist of single cells

• Molecular cell biology brings together biochemistry, biophysics, molecular biology, microscopy, genetics physiology, computer science, and developmental biology

1.1 - The Diversity and Commonality of Cells

• Cells come in different varieties of shapes and sizes

• Some move really fast and have fast-changing structures

• Others are largely stationary and structurally stable

• Oxygen kills some cells but is an absolute requirement for others

• Most cells in multicellular organisms are intimately involved with other cells

• Some unicellular organisms live in isolation, others form colonies or live in close association with other types of organisms

• All cells share certain structural features and carry out many complicated processes in common ways

All Cells are Prokaryotic or Eukaryotic

• Prokaryotic

  • Consist of a single closed compartment that is surrounded by the plasma membrane, lack a defined nucleus, has a relatively simple internal organization

  • Bacteria is an example, cyanobacteria or blue-green algae can be unicellular or filamentous chains of cells

  • Bacterial cells don’t have membrane-bounded compartments, many proteins are precisely localized in their aqueous interior

  • Cytosol - an indication of the presence of the internal organization

  • A single Escherichia coli bacteria has a dry weight of about 25 x 10 -14

  • Bateria account for an estimated 1-1.5 kg of the average human’s weight

  • 5 x 1030 is the estimated amount of bacteria on Earth and a total of 1012kg

  • These cells have been found 7 miles deep in the ocean and 40 miles up in the atmosphere proves that they are adaptive

  • Carbon stores in bacteria is nearly as much as the carbon stored in plants

• Eukaryotic

  • Contain a defined membrane-bound nucleus and extensive internal membranes which enclose other compartments - organelles

  • The cytoplasm is the region between the plasma membrane and the nucleus comprising the cytosol (aqueous phase) and the organelles

  • Comprise all members of the plant and animal kingdoms (including fungi) which exist in both multicellular (molds) and unicellular (yeasts) and protozoans

  • These cells are commonly about 10-100 μm across multiple similarities

  • During recent years detailed analysis of DNA sequences has formed varieties of the prokaryotic organisms have revealed two distinct types

    • “True” bacteria / eubacteria

    • Archaea ( archaebacteria or archaeans)

  • Researchers have developed evolutionary lineage trees

  • According to those trees, the archaea and the eukaryotes diverged from the true bacteria before they diverged from each other

• Many archaeans grow in unusual extreme environments that may resemble ancient conditions when life first appeared on Earth

Unicellular Organisms Help and Hurt Us

• Bacteria and archaebacteria are the most abundant single-celled organisms

  • Are commonly 1-2 μm in size

• These are remarkable biochemical factories converting simple chemicals into complex biological molecules

• Some major diseases caused by bacteria

  • Mycobacterium tuberculosis, anthrax from Bacillus anthracis, cholera from Vibrio cholera, food poisoning from certain types of E. coli and Salmonella

• Humans are walking repositories of bacteria (plants and animals)

• We have bacteria inside us such as in our intestines, bacteria help us digest food and in turn, they are able to reproduce

• E coli is a common gut bacterium and a great experimental organism

• Intestinal cells form appropriate shapes providing a niche where the bacteria can live

  • Facilitating proper digestion by the combined efforts of the bacterial and intestinal cells

• Peaceful mutualism of humans and bacteria can be violated by one or both

• When bacteria begin to grow in places where they are dangerous to us the cells of our immune system fight back

• Powerful antibiotic medicines (selectively poison prokaryotic cells) provide rapid assistance to our (slow-developing) immune response

• Protozoa benefit the food chain, they fertilize the soil, control the population of bacteria and excrete nitrogenous and phosphate compounds, and in waste treatment systems (natural and man-made)

• Unicellular eukaryotes are critical for marine ecosystems, consume large quantities of phytoplankton, harbor photosynthetic algae, use sunlight to produce biologically useful energy forms and small fuel molecules

• Some protozoa do give us grief: Entamoeba, histolytica causes dysentery; Trichomonas vaginalis, vaginitis; and Trypanosoma brucei, sleeping sickness

• Each year Plasmodium falciparum and related species cause more than 300 million new cases of malaria

• They inhabit mammals and mosquitoes changing their morphology and behavior in response to signals in each of their environments

• Yeasts and molds (collectively constitute the fungi) are important for breaking down plant and animal remains for reuse

  • They make numerous antibiotics and manufacture bread, beer, wine, and cheese

• Fungal diseases, which range from relatively innocuous skin infections, such as jock itch and athlete’s foot, to life-threatening Pneumocystis carinii pneumonia, a common cause of death among AIDS patients

Single Cells Can Have Sex

• Saccharomyces cerevisiae (common yeast)

• Many unicellular organisms yeats have two mating types that are conceptually like a male and female gametes (eggs and sperm) of higher organisms

• Two yeast cells of opposite mating types can fuse or mate

• Sexual life cycles allow more rapid changes in the genetic inheritance that would be possible without having sex

Viruses Are the Ultimate Parasites

• Viruses cause diseases; chickenpox, influenza, pneumonia (some types, polio, measles, rabies, hepatitis, the common cold)

• Viral infections in plants have a major economic impact on crop production

• Viruses are not considered alive because they can’t grow nor reproduce on their own

• For survival, a virus must infect a host cell and take over its internal machinery to synthesize viral proteins and (in some cases) replicate the viral genetic material

• When newly made viruses are released the cycle starts anew

• Viruses are much smaller than cells (virus - 100nm in diameter, cell - 1000nm)

• The virus is composed of a protein coat that encloses a core containing the genetic material which carries the information for producing more viruses

• The coat protects a virus from the environment and allows it to stick to or enter specific host cells

• In some viruses, the protein coat is surrounded by an outer membrane-like envelope

• The ability of viruses to transport genetic material into cells and tissues represents a medical menace and a medical opportunity

• Viral infections can be devastatingly destructive causing cells to break open and tissues to fall apart

• Many methods for manipulating cells depend upon using viruses to convey genetic material into cells

• To do this, the portion of the viral genetic material that is potentially harmful is replaced with other genetic material, including human genes

• The altered viruses (or vectors) still can enter cells toting the introduced genes with them

• One day, diseases caused by defective genes may be treated by using viral vectors to introduce a normal copy of a defective gene into patients

• Current research is dedicated to overcoming the considerable obstacles to this approach, such as getting the introduced genes to work at the right places and times

We Develop From a Single Cell

• In 1827, Karl von Baer discovered that mammals grow from eggs that come from the mother’s ovary

• Fertilization of an egg by a sperm cell yields a zygote a visually unimpressive cell 200 μm in diameter

• Every human being begins as a zygote, which houses all the necessary instructions for building the human body containing about 100 trillion (1014) cells

• Development begins with the fertilized egg cell dividing into two, four, then eight cells, forming the very early embryo

• Continued cell proliferation and then differentiation into distinct cell types give rise to every tissue in the body

• One initial cell, the fertilized egg (zygote), generates hundreds of different kinds of cells that differ in contents, shape, size, color, mobility, and surface composition

• Making different kinds of cells—muscle, skin, bone, neuron, blood cells—is not enough to produce the human body

• The cells must be properly arranged and organized into tissues, organs, and appendages

• Our two hands have the same kinds of cells, yet their different arrangements—in a mirror image—are critical for function

• In addition, many cells exhibit distinct functional and/or structural asymmetries, a property often called polarity

• From such polarized cells arise asymmetrically, polarized tissues such as the lining of the intestines and structures like hands and hearts

Stem Cells, Cloning, and Related Techniques Offer Exciting Possibilities but Raise Some Concerns

• Identical twins occur naturally when the mass of cells composing an early embryo divides into two parts, each of which develops and grows into an individual animal

• Each cell in an eight-cell-stage mouse embryo has the potential to give rise to any part of the entire animal

• Cells with this capability are referred to as embryonic stem (ES) cells

• ES cells can be grown in the laboratory (cultured) and will develop into various types of differentiated cells under appropriate conditions

• The ability to make and manipulate mammalian embryos in the laboratory has led to new medical opportunities as well as various social and ethical concerns

• In vitro fertilization allows many otherwise infertile couples to have children

• A new technique involves extraction of nuclei from defective sperm incapable of normally fertilizing an egg, injection of the nuclei into eggs, and implantation of the resulting fertilized eggs into the mother

• In recent years, nuclei taken from cells of adult animals have been used to produce new animals

• In this procedure, the nucleus is removed from a body cell (e.g., skin or blood cell) of a donor animal and introduced into an unfertilized mammalian egg that has been deprived of its own nucleus

• This manipulated egg, which is equivalent to a fertilized egg, is then implanted into a foster mother

• The ability of such a donor nucleus to direct the development of an entire animal suggests that all the information required for life is retained in the nuclei of some adult cells

• All the cells in an animal produced in this way have the genes of the single original donor cell, the new animal is a clone of the donor

• Repeating the process can give rise to many clones

• The majority of embryos produced by this technique of nuclear-transfer cloning do not survive due to birth defects

• Even those animals that are born live have shown abnormalities, including accelerated aging

• The “rooting” of plants, in contrast, is a type of cloning that is readily accomplished by gardeners, farmers, and laboratory technicians

• The technical difficulties and possible hazards of nuclear-transfer cloning have not deterred some individuals from pursuing the goal of human cloning

• Cloning of humans per se have very limited scientific interest and is opposed by most scientists because of its high risk

• Of greater scientific and medical interest is the ability to generate specific cell types starting from embryonic or adult stem cells

• The scientific interest comes from learning the signals that can unleash the potential of the genes to form a certain cell type

• The medical interest comes from the possibility of treating the numerous diseases in which particular cell types are damaged or missing

1.2 - The Molecules of a Cell

• Molecular cell biologists explore how all the remarkable properties of the cell arise from underlying molecular events: the assembly of large molecules, binding of large molecules to each other, catalytic effects that promote particular chemical reactions, and the deployment of information carried by giant molecules

Small Molecules Carry Energy, Transmit Signals, and Are Linked into Macromolecules

• Much of the cell’s contents is a watery soup flavored with small molecules (e.g., simple sugars, amino acids, vitamins) and ions (e.g., sodium, chloride, calcium ions)

• The locations and concentrations of small molecules and ions within the cell are controlled by numerous proteins inserted in cellular membranes

• These pumps, transporters, and ion channels move nearly all small molecules and ions into or out of the cell and its organelles

• One of the best-known small molecules is adenosine triphosphate (ATP), which stores readily available chemical energy in two of its chemical bonds

• When cells split apart these energy-rich bonds in ATP, the released energy can be harnessed to power an energy-requiring process like muscle contraction or protein biosynthesis

• To obtain energy for making ATP, cells break down food molecules

  • For example: when sugar is degraded to carbon dioxide and water, the energy stored in the original chemical bonds is released and much of it can be “captured” in ATP

• Bacterial, plant, and animal cells can all make ATP by this process

• Plants and a few other organisms can harvest energy from sunlight to form ATP in photosynthesis

• Other small molecules act as signals both within and between cells; such signals direct numerous cellular activities

• The powerful effect on our bodies of a frightening event comes from the instantaneous flooding of the body with epinephrine, a small-molecule hormone that mobilizes the “fight or flight” response

• The movements needed to fight or flee are triggered by nerve impulses that flow from the brain to our muscles with the aid of neurotransmitters

• Certain small molecules (monomers) in the cellular soup can be joined to form polymers through the repetition of a single type of chemical linkage reaction

• Cells produce three types of large polymers, commonly called macromolecules: polysaccharides, proteins, and nucleic acids

• These macromolecules are critical structural components of plant cell walls and insect skeletons

• A typical polysaccharide is a linear or branched chain of repeating identical sugar units

• Such a chain carries information: the number of units

• If the units are not identical, then the order and type of units carry additional information

• Some polysaccharides exhibit the greater informational complexity associated with a linear code made up of different units assembled in a particular order

• This property, however, is most typical of the two other types of biological macromolecules—proteins and nucleic acids

Proteins Give Cells Structure and Perform Most Cellular Tasks

• The varied, intricate structures of proteins enable them to carry out numerous functions

• Cells string together 20 different amino acids in a linear chain to form a protein

• Proteins commonly range in length from 100 to 1000 amino acids, but some are much shorter and others longer

• We obtain amino acids either by synthesizing them from other molecules or by breaking down the proteins that we eat

• The “essential” amino acids, from a dietary standpoint, are the eight that we cannot synthesize and must obtain from food

• Beans and corn together have all eight, making their combination particularly nutritious

• Once a chain of amino acids are formed, it folds into a complex shape, conferring a distinctive three-dimensional structure and function on each protein

• Some proteins are similar to one another and therefore can be considered members of a protein family

• A few hundred such families have been identified

• Most proteins are designed to work in particular places within a cell or to be released into the extracellular (extra, “outside”) space

• Elaborate cellular pathways ensure that proteins are transported to their proper intracellular (intra, within) locations or secreted

• Proteins can serve as structural components of a cell, (by forming an internal skeleton)

• They can be sensors that change shape as temperature, ion concentrations, or other properties of the cell change

• They can import and export substances across the plasma membrane

• They can be enzymes, causing chemical reactions to occur much more rapidly than they would without the aid of these protein catalysts

• They can bind to a specific gene, turning it on or off

• They can be extracellular signals, released from one cell to communicate with other cells, or intracellular signals, carrying information within the cell

• They can be motors that move other molecules around, burning chemical energy (ATP) to do so

• Seems impossible at first glance

• But if a “typical” protein is about 400 amino acids long, there are 20400 possible different protein sequences

• Even assuming that many of these would be functionally equivalent, unstable, or otherwise discountable, the number of possible proteins is well along toward infinity

• How many protein molecules a cell needs to operate and maintain itself?

  • To estimate this number, let’s take a typical eukaryotic cell, such as a hepatocyte (liver cell)

  • This cell, roughly a cube 15 μm (0.0015 cm) on a side, has a volume of 3.4 x 10-9 cm3 (or milliliters), assuming a cell density of 1.03 g/ml, the cell would weigh 3.5 x 10-9 g

• Since protein accounts for approximately 20 percent of a cell’s weight, the total weight of the cellular protein is 7 x 10-10 g

• The average yeast protein has a molecular weight of 52,700 (g/mol)

• Assuming this value is typical of eukaryotic proteins, we can calculate the total number of protein molecules per liver cell as about 7.9 x 109 from the total protein weight and Avogadro’s number, the number of molecules per mole of any chemical compound (6.02 x 1023)

• To carry this calculation one step further, consider that a liver cell contains about 10,000 different proteins; thus, a cell contains close to a million molecules of each type of protein on average

• In actuality, the abundance of different proteins varies widely, from the quite rare insulin-binding receptor protein (20,000 molecules) to the abundant structural protein actin (5 x 108 molecules)

Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place

• The information about how, when, and where to produce each kind of protein is carried in the genetic material, a polymer called deoxyribonucleic acid (DNA)

• The three-dimensional structure of DNA consists of two long helical strands that are coiled around a common axis, forming a double helix

• DNA strands are composed of monomers called nucleotides; these often are referred to as bases because their structures contain cyclic organic bases

• Four different nucleotides, abbreviated A, T, C, and G, are joined end to end in a DNA strand, with the base parts projecting out from the helical backbone of the strand

• Each DNA double helix has a simple construction: wherever there is an A in one strand there is a T in the other, and each C is matched with a G

• This complimentary matching of the two strands is so strong that if complementary strands are separated, they will spontaneously zip back together in the right salt and temperature conditions

• Such hybridization is extremely useful for detecting one strand using the other

  • For example, if one strand is purified and attached to a piece of paper, soaking the paper in a solution containing the other complementary strand will lead to zippering even if the solution also contains many other DNA strands that do not match

• The genetic information carried by DNA resides in its sequence, the linear order of nucleotides along a strand

• The information-bearing portion of DNA is divided into discrete functional units, the genes, which typically are 5000 to 100,000 nucleotides long