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Over its brief 30-year history, cell biology has matured into a vigorous and rapidly expanding discipline. Today, it forms an essential bridge between important basic fields such as biochemistry, developmental biology, physiology, neurobiology, molecular genetics, immunobiology and microbiology. Since cell biology focuses on the functions of cells in diverse contexts, it also provides a natural connection between basic biological research and medicine.
CONTENTS
The Cell / Cellular Chemistry / Nucleus and Chromosomes / Nucleic Acid and Protein Synthesis / Cell Membranes / Protein and Vesicular Traffic / Receptors and Second Messengers / Energy, Mitochondria, and Chloroplasts / Cytoskeleton and Cell Movement / Extracellular Matrix and Cell-Cell Interactions / The Cell Cycle / Cancer and Cell Death / Development and Differentiation / Gene Expression in Eukaryotes and Prokaryotes / Techniques in Cell Biology / Answers to Self-Testing Questions / Glossary
 about Organelles
Cell Biology - Topics by organelle system, as part of the interactive learning program at the University of Arkansas for Medical Sciences, Little Rock, AR.
Golgi Apparatus - Introduction to the intracelullar post office, and it's functions, with electron micrograph, from school student in UK.
Golgi Bodies - Electron micrographs, cartoons and explanations of endoplasmic reticulum, the apparatus and their function, from The Natural Toxins Reaseach Center, Texas A&M University, Kingsville.
Malhotra Lab - Studies vesicular transport and Golgi apparatus at the cellular and molecular level. Includes biochemistry, histology and micrographs performed in La Jolla, CA.
Neurohistology Lab - Nucleus, cytoplasm, neuroglia, neuronal processes and fiber terminations of nerves, with flash-dependent electron micrographs, and explanation of their function from the Computer Assisted Teaching System of the University of Vermont, Burlington.
Peroxins - Introduction to the function, phylogenetics and association with human peroxisome biogenesis disorders, and access to an annotated database of Peroxins, and link to cv of author in Nottingham, UK.
The Cell - The structural components and their cellular functions; centrosome, ribosomes, mitochondria, golgi complex, lisosomes, endoplasmic reticulum, chloroplast, vacuoles, cilium andflagellum, with illustrations of the cytoskeleton and cytoplasmic membrane, from
The Peroxisome Website - Information about the peroxisome and associated disorders for people of all scientific backgrounds, from patients to scientists.
Links about Cell Membrane and Adhesion:
CEA The Carcinoembryonic Antigen Family - Comprehensive structural and immunological information on membrane-bound proteins involved in adhesion. Includes molecule cartoons of human, mouse, rat and other species. Details of conference in Frauenchiemsee, Germany.
Cell Junctions - Adhesion and desmosomes research at New York University School of Medicine.
Green, Kathleen J. - Overview of research on adhesion, its role in embryogenesis, differentiation and wound healing. Includes research opportunities, training at Northwestern University Medical School, Chicago, IL.
Integrin - Family of transmembrane proteins involved in the extracellular matrix. Includes classification, ligands, structure images, realted links, discussion forum and guest book.
Thorkild's Lectin Page - Resources introducing the lectins, and research devoted their functions, maintained at University of Copenhagen, Denmark.
dictyBase - Dictyostelium discoideum as a model for cellular development, chemotaxis, motility, cytokinesis defects, phagocytosis and functional genomics, at the Northwestern University Medical School, Chicago, IL.
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Stereomicroscope
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Topic 1
The Cell
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Identified by Robert Hook(1665)
- Cell Theory :
All organisms consist of one or more cells.
The cell is the basic unit of structure for all organisms.
All cells arise only from presxisting cells.
- Schleiden developed cell theory for plants while Schwarm did the same for animals (1838-1839).
- Rudolf Virchow (1855); "omnis cellula e cellula"
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The Prokaryotic and Eukaryotic cells:
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Topic 2
Cellular Chemistry
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The Chemistry of Cells
- Carbohydrates include simple sugars and polysaccharides. Polysaccharides serve as storage forms of sugars, structural components of cells, and markers for cell recognition processes. Glucose can be synthesized from other organic molecules, using energy and reducing power in the forms of ATP and NADPH, respectively.
- Lipids are the principal components of cell membranes, and they serve as energy storage and signaling molecules. Phospholipids consist of two hydrophobic fatty acid chains linked to a hydrophilic phosphate-containing head group. Lipids are synthesized from acetyl CoA, which is formed from the breakdown of carbohydrates.
- Nucleic acids are the principal informational molecules of the cell. Both DNA and RNA are polymers of purine and pyrimidine nucleotides. Hydrogen bonding between complementary base pairs allows nucleic acids to direct their self-replication. Purine and pyrimidine nucleotides are synthesized from carbohydrates and amino acids.
- Proteins are polymers of 20 different amino acids, each of which has a distinct side shain with specific chemical properties. Each protein has a unique amino acid sequence, which determines its three-dimentional structure.
- Enzymes - All chemical reactions within cells are catalyzed by enzymes. Metabolic Energy - Free energy and ATP : ATP serves as a store of free energy, which is used to drive energy-requiring reactions within cells.
- Phospholipids
- Triglycerides
- Cellulose
- Phosphate
- Hydrocarbon
- ATP
- Purine
- Deoxyribonucleotides
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Topic 3
Nucleus and Chromosome
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세포핵과 염색체의 구조와 기능
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Topic 4
Nucleic Acid and Protein Synthesis
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핵산과 단백질 합성
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Topic 6
Protein and Vesicular Traffic
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골지체, 소포체, 리소좀의 구조와 기능
- Cellular Organelles
1. Endoplasmic Reticulum
Within the cytoplasm of cells is a 3-dimensional maze of connecting and branching channels made by a continuous membrane. This is called the endoplasmic reticulum (ER). ER can be classified as rough ER when ribosomes are attached to the cytosolic side of the membrane or smooth ER when no ribosomes are present. Rough ER is prominent in cells that
are making proteins for export such as digestive enzymes, hormones, structural proteins or antibodies. The main function of rough ER is the segregation of proteins destined for export from the cell or for intracellular use. Proteins are modified within the ER by the addition of carbohydrate, removal of a signal sequence and other post-translational modifications. Phospholipid synthesis and assembly of
multichain proteins also occur there.
Smooth ER lacks attached ribosomes and often appears more tubular than rough ER. The two types of ER are continuous in some sections. Smooth ER confers on the cell the ability to perform a variety of specialized functions. It is necessary for steroid sysnthesis, metabolism and detoxification of substances in the liver, phospholipid synthesis, and
excitation-contraction coupling in skeletal muscle.
2. Golgi complex
The Golgi, a curved membrane stack resembling a stack of pancakes, finishes the post-transitional modifications, concentrates and packages proteins for export or storage. It also adds directions for the destination of the protein package. Proteins made within the rough ER bud off in vesicles and are trasported to the Golgi where the vesicles fuse with the membrane and the components are further modified,
concentrated and packaged by the time they bud off as vesicles on the opposite side of the the Golgi. Therefore, the Golgi shows a polarity in that one side accepts incoming vesicles (convex or cis face) and the final product vesicles bud off the opposite side (concave or trans face). In fact, biochemical studies have shown that the enzymes present
within the Golgi are different at different levels of the membrane stack.
3. Lysosomes
Lysosomes are membrane bound vesicles (0.05 to 0.5 micron) containing more than 40 hydrolytic enzymes that can digest most biological macromolecules. These organelles are the sites of intracellular digestion that are more numerous in cells performing phagocytosis. The limiting membrane keeps the digestive enzymes separate from the cytoplasm. The most common lysosomal enzymes are acid phosphatase, ribonuclease, deoxyribonuclease, proteases, sulfatases, and lipases. The
enzymes function optimally at pH 5 and are mostly inactive at the pH of the cytosol (7.2). This taken with the limiting membrane protects the cell from digesting itself. Lysosomal enzymes are synthesized on the rough ER, trasferred to the Golgi for modification and packaging. The cellular machinery attaches a directional signal to the enzymes (mannose-6-phosphate) that allows the ER and Golgi to sort these proteins and, via a receptor mediated process, segregate them to forming lysosomes.
Primary lysosomes are small concentrated sacs of enzymes that are not digesting anything. Primary lysosomes fuse with a phagocytic vacuole to become secondary lysosomes or phagolysosomes where digestion begins. As the substances are digested the nutrients diffuse through the lysosomal
membrane to the cytosol. Residual bodies are formed when indigestable things remain in the vacuoles. In cells with a long life span such as cardiac muscle cells, residual bodies are more numerous and are referred to lipofuscin or age pigment.
Lysosomes also participate in the turnover of cellular organelles. Cytoplasmic components become enclosed in a membrane that fuses with a primary lysosome to become an autophagosome. In bone, the lysosomal enzymes are released from osteoclasts to digest surrounding bone during the process of remodeling. Lysosomal enzymes are also involved in the
process of inflammation.
4. Peroxisomes
These small (0.5 to 1.2 microns) containing oxidative enzymes. Peroxisomes contain amino oxidases, hydroxyacid oxidase and catalase. Catalase protects the cell from hydrogen peroxide damage. Enzymes involved in lipid metabolism are also found in peroxisomes. Peroxisomal enzymes are synthesized on the free cytosolic ribosomes with a signal sequence that directs them to peroxisomes. As enzymes are added the peroxisome grows and then splits into two smaller peroxisomes.
- Secretory Granules
Secretory granules are found in cells that store products until stimulated to release them as in hormones, neurotransmitters or digestive enzymes. These membrane bound vesicles contain a concentrated from of the prarticular secretory product.
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Topic 7
Receptors and Second Messengers
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수용체와 2차 정보전달자
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Topic 8
Energy, Mitochondria, and Chloroplast
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에너지, 미토콘드리아, 엽록체
- 1. Mitochondia
These organelles are the power houses of the cell and contain the molecular machinery for the conversion of energy from the breakdown of glucose into adenosine triphosphate (ATP), the energy currency of the cell. The energy stored in the high energy phosphate bonds of ATP is then available to power cellular functions. Mitochondria are mostly protein, but some lipid, DNA and RNA are present. The unique structure
of these organelles can be seen under the electron microscope. These generally spherical organelles have an outer membrane surrounding an inner membrane that folds (cristae) into a scaffolding for oxidative phosphorylation and electron transport enzymes. Most mitochondria have flat shelf-like cristae, but those in steroid secreting cells may have
tubular cristae. The mitochondiral matrix contains the enzymes of the citric acid cycle, fatty acid oxidation and mitochondrial nucleic acids.
Mitochondiral DNA is double standed and circular. Mitochndrial RNA comes in the three standard varieties; ribosomal, messenger and transfer, but each is specific to the mitochondria. Some protein synthesis occurs in the mitochondria on mitochondrial ribosomes that are different than cytoplasmic ribosomes. Other mitochondrial proteins are made on cytoplasmic ribosomes with a signal peptide that directs them to the mitochondria. The metabolic activity of the cell is related to the number of cristae and the number of mitochondria within a cell. Cells with alot of metabolic activity, such as heart muscle, have many well developed mitochondria. New mitochondria are formed from preexisting
mitochondria when they grow and divide.
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Topic 9
Cytoskeleton and Cell Movement
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세포골격과 세포운동
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Topic 10
Extracellular Matrix and Cell-Cell Interactions
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세포외 기질, 세포와 세포의 상호작용
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Topic 11
The Cell Cycle
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세포주기
- 1. 세포분열 細胞分裂 (cell division)
보통 핵분열이 세포질분열보다 먼저 일어난다. 이 핵분열은 대부분의 경우 유사분열이며, 유사분열은 염색체의 분배와 같은 중요한 일을 한다. 체세포분열과 감수분열 양쪽에서 보인다. 체세포분열의 핵분열은 전기 ·중기 ·후기 ·말기로 나누어진다. 분열 결과 만들어진 딸세포들은 모세포와 동일하며, 핵내의 유전물질은 정확하게 복제되어 2개의 딸세포로 나누어져 들어간다. 감수분열은 생식세포를 형성할 때 일어나는 분열로서, 그 결과 염색체의 수가 체세포에 비하여 반으로 감소한다. 그리고 체세포분열의 핵분열에 앞서 이형핵분열인 제1분열이 존재한다.
세포분열 과정을 살펴보면, 분열에서 다음 분열까지의 시기를 간기(間期) 또는 휴지기라고 한다. 이 간기에는 세포내의 물질대사나 고분자합성이 일어나고, DNA 등의 염색체 물질의 복제도 일어난다. 분열 직후 형성된 딸세포는 간기에 점차 커져 핵도 2배로 자란다. 간기 기간은 동물 ·식물 ·종 ·품종 ·조직 ·기관의 차이, 온도 ·영양 등에 따라 다르며, 수 시간 또는 수십 시간에 이르는 경우가 많다. 간기의 핵은 핵분열을 안 할 뿐 물질대사는 왕성하다. 유사분열에 의해 염색체가 2개의 핵으로 나누어진 후 세포질분열이 일어난다. 분열기에 들어서면 우선 핵이 전기 ·중기 ·후기 ·말기를 거쳐 딸세포가 형성된다.
- ① 전기:핵 안의 염색사(染色絲)가 나선형으로 꼬여 두껍고 짧아져 끈 모양의 염색체가 된다. 염색체는 2개의 염색분체가 붙어 있는 모양으로 되어 있으며, 동시에 핵막 ·인이 소실된다. 고등식물을 제외한 대부분의 세포들은 한 쌍의 중심립이 핵막 바깥쪽에 위치한다. 중심립은 먼저 분열한 후 이동을 시작하여 양극에 도달한다. 중심체가 없는 세포에서는 양극으로부터 방추체가 생기기 시작하는데, 이를 극모(極帽)라 한다. 동시에 양극 또는 중심체를 중심으로 하여 별빛 모양 또는 실 모양 구조를 통틀어 성상체라고 한다. 유사분열기간 중 전기가 가장 긴 시간을 차지한다.
- ② 중기:구형인 핵이 타원형이 되며 비염색질은 방추형의 방추체를 이루면서 적도면(赤道面:적도판)을 향하여 염색체가 이동한다. 염색체는 적도판에 늘어서서 각각 정렬하며, 각 염색체의 동원체와 방추체의 양극을 묶는 방추사가 생긴다. 각 염색체의 동원체는 방추사와 연결되어 양 극으로 이동할 준비를 한다. 이 때가 염색체 관찰의 가장 좋은 시기이다.
- ③ 후기:염색분체가 나누어져 각각의 염색체로 되어 양극으로 끌려 간다. 염색체가 이동할 때는 방추사와 연결된 동원체 부분부터 끌려가며, 염색체 가닥이 뒤따르게 된다.
- ④ 말기:극에 도달한 염색체는 차츰 풀어져 염색사로 되어 관찰하기 어렵게 된다. 딸염색체군을 바탕으로 해서 2개의 딸핵이 형성된다. 즉, 방추사가 사라지면서 핵막과 인은 다시 나타나 딸핵은 다시 간기의 핵 모양으로 된다. 식물에서는 후기와 말기 사이에 적도면에 세포판이 생기고 격막을 형성하여 모세포가 2개의 딸세포로 나뉜다. 동물에서는 적도면 주위에서 모세포가 잘려 세포질을 분할한다. 또, 동물세포에서는 전기와 중기 사이에 중심체가 핵 바깥에 나타나 2분되어 두 극을 만든다. 이상과 같이 생식세포가 생길 때의 감수분열에서는 간기가 길고 분열 후 염색체수가 반감한다. 염색체가 형성되지 않고 갑자기 핵이 둘 또는 그 이상의 덩어리로 떨어져 나뉘는 분열이 있는데 이것은 병적인 세포 ·조직 또는 집합핵 등이 분열할 때 볼 수 있다.
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Topic 12
Cancer and Cell Death
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암, 세포고사
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Topic 13
Development and Differentiation
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발생과 분화
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Topic 15
Techniques
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The discovery and study of cells was dependent on the development of the microscope. Further refinements and adaptations have allowed study of subcellular components at the molecular level. Here, we review some of the common methods used to study cells and tissues. Microscopy Under the standard light microscope thin sections of tissues are examined by transillumination. Light is passed through a condenser that collects the light into a focused beam that then passes through the specimen and is collected by an objective lens that magnifies the image (anywhere from 4X to 200X). The specimen is viewed through an ocular lens that also magnifies the image (usually 4X). The total magnification is obtained by multiplying the magnifying power of the objective and ocular lenses. Image quality is dependent on the resolving power of the microscope, which is largely determined by the quality of the objective lens. The light microscope has a limiting resolution of about 0.1 micron (objects smaller than this cannot be resolved) which allows a magnification of over 1000X without a loss of quality. Often a camera is attached to the microscope via a separate port so that pictures can be taken while viewing through the ocular. Very sensitive video cameras are used to capture and transfer digital images to computer programs for image analysis. Most cells and tissues in their natural state contain little pigment that would absorb light. Therefore, they are normally translucent to transmitted light and little detail can be seen. Consequently, methods have been developed to stain cells, subcelular components and tissue components and structures. Most classical stains require a fixed or preserved specimen. Preservation of the specimen is necessary to preserve cellular structures in a "natural" state against intracellular digestion and desiccation. When tissues or cells must be thinly sectioned, the aqueous environment is replaced by a resin or embedding media such as paraffin or epoxy that penetrates the cell and adds rigidity to the tissue. These embedding media are usually not hydrophillic and sometimes lipids are removed. To limit the loss of lipids or study enzyme activity, sometimes the tissues are cut when frozen rather than fixing and embedding them. In the ideal tissue preparation the tissue retains the same structure and molecular composition as the living tissue. This is very rare and usually artifacts from the preparation process are present. Phase Contrast Microscopy can be used to image transparent cells. The principle behind this type of microscopy is that light changes speed and direction when passing through cellular and extracellular structures of different refractive indices. This causes some structures to appear lighter or darker relative to each other. A modification of this is Normarski Differential Interference Microscopy that uses polarized light and gives a three dimensional look at transparent objects. Confocal microscopy uses lasers and computers to produce three-dimensional images of living cells and tissue slices. Optical sections of the specimen are collected by laser scanning and stored in the computer. The information from each visual plane can be viewed and reconstructed into three dimensional projections of the specimen. Fluorescence Microscopy utilizes substances (fluorophores) that, when irradiated by a certain wavelength of light emit light of a longer wavelength. Tissue sections are usually irradiated with ultraviolet light so that the emission is in the visible portion of the spectrum. The microscope used has a strong ultraviolet light source and special filters that eliminate ultraviolet light before it gets to the observers eyes. Some fluorescent compounds have an affinity for nucleic acids allowing the localization of nucleic acids with cells. Others are are specific for the mitochondria. Fluorescent probes can be made by chemically coupling the fluorophor to a relevant molecule such as a hormone or antibody. Electron Microscopy is based on the interaction of electrons with tissue components and electron dense stains. The electron microscope is capable of 0.1 nanometer resolution. Magnifications can be as much as 400 times greater than those achieved in light microscopy. The principle behind transmission electron microscopy or TEM is that an electron beam is passed through a stained ultrathin section of a tissue that has been embedded in plastic. The thin sections are cut with diamond or glass knives and mounted on metal grids prior to staining. The electron dense stain (lead or uranium) is differentially taken up by the cellular structures and therefore the electrons are absorbed more by some structures than others. The electrons that pass through the specimen fall on a photographic film or digital image plate to form an image. Scanning electron microscope permits pseudo-three-dimensional views of the surface of specimens. Specimens are covered with an electron dense material and a narrow electron beam in passed over the surface. At each point, the electron beam produces emitted electrons from the metal coating of the specimen. A detector captures these emitted electrons and the brightness of a synchronous cathode ray tube is modified to produce a three dimensional image that has highlights and shadows. Cell & Tissue Culture Cell and tissue culture allows for the direct study of cell behavior in vitro . Chemically defined media, growth factors, hormones and serum components simulate the normal environment in a culture dish. Infectious agents such as protozoa and viruses that grow only within cells can be studied using cell culture techniques. Cells are collected by enzymatic or mechanical disruption of tissues and isolated to culture media as suspension or contact dependent cultures. Normal cells have finite, genetically programmed life span. However, transformed cells such as those found in cancer, become immortal cell lines and can go through many more cell divisions and have a much longer life. Cells can be harvested and frozen in liquid nitrogen for later reconstitution and use in cell culture experiments. Cell Fractionation Separation of cellular components from one another is accomplished by differential centrifugation. Centrifugal force is used to separate organelles and cellular components as a function of their sedimentation coefficients. The coefficient is based on the size, form, and density of the particle. Cells are mechanically lysed and the homogenate is subjected to successive centrifugation at increasing speeds. At each step the resultant pellet contains a different cellular component and the supernatant is collected for the next step. For instance, the first step might pellet the nuclei leaving the other cellular components in the supernatant. After the second step mitochondria and lysosomes are collected in the pellet and the supernatant subjected to the next spin. The size and density of the cellular components in the pellet decreases with each step in the process. Cell fractionation allows detailed study of cellular components obtained in a relatively pure state. Immnocytochemistry Immunocytochemical methods allow the study of the presence and activity of specific macromolecules in cells and tissues. Antigen-antibody, and receptor-hormone interactions are exploited by the labeling of proteins with fluorescent molecules, enzymes or electron dense molecules. These labels make the molecule visible in the microscope without causing a loss of the protein's biologic activity. Labeled antibodies or hormones bind only to their antigens or receptors, respectively, thereby permitting localization of specific antigens in tissue specimens. In direct immunocytochemistry, an antibody is made specific to the antigen. The more sensitive indirect approach uses an unlabeled primary antibody to the antigen and a labeled secondary antibody that binds to the primary antibody and makes the complex visible under the microscope.
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Life can exist only where molecules and cells remain organized. Energy is needed by all cells to maintain organization. Physicists define energy as the ability to do work; in this case, the work is the continuation of life itself. The behavior of energy has been expressed in terms of reliable observations known as the laws of thermodynamics. There are two laws of thermodynamics. The first law states that energy can neither be created nor destroyed. This law implies that the total amount of energy in a closed system (for example, the universe) remains constant. Energy neither enters nor leaves a closed system. Within a closed system, energy can change, however. For instance, the chemical energy in gasoline is released when the fuel combines with oxygen and a spark ignites the mixture within an automobile's engine. The gasoline's chemical energy is transformed into heat energy, sound energy, and the energy of motion. The second law of thermodynamics states that the amount of available energy in a closed system is decreasing constantly. This loss of available energy is referred to as entropy, which is defined as the degree of disorder or randomness of a system. The entropy of any closed system is constantly increasing because energy, such as beat energy, is being lost. In essence, any closed system tends toward disorganization. Every movement of the body, every thought, and every chemical reaction in the cells involves a shift of energy and a measurable loss of energy in the process. Unfortunately, the transfers of energy in living systems are never completely efficient. For this reason, considerably more energy must be taken into the system than is necessary to carry out the actions of life.
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Class is one and half hour long
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Includes one hour weekly drill
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