01.Cell Biology I (1).pdf

Cell Biology The cell is the functional and morphological unit of living organisms. Unicellular organisms are made up of one cell, while multicellular organisms are made up of several cells grouped together and specialized in certain functions within the organism itself. Eukaryotic cells are muc...

Cell Biology The cell is the functional and morphological unit of living organisms. Unicellular organisms are made up of one cell, while multicellular organisms are made up of several cells grouped together and specialized in certain functions within the organism itself. Eukaryotic cells are much more evolved and complex cells than prokaryotes (bacteria). They have a larger size, a differentiated nucleus with a more complex DNA and contain numerous organelles. Human cells have differentiated and specialized in certain functions. In the human body we will find many different types of cells, each with a particular function. Cells that resemble each other, or that serve the same purpose, are grouped together forming tissues. Tissues will be organized in different organs and systems. Animal eukaryotic cell 1. 2. 3. 4. 5. Nucleolus Nucleus Ribosome Granules Rough endoplasmic reticulum (RER) 6. Golgi apparatus 7. Cytoskeleton 8. Smooth endoplasmic reticulum (SER) 9. Mitochondria 10. Vesicles 11. Cytosol 12. Granules 13. Centriole Although each type of cell has a specific function, they will all have common characteristics. They are all surrounded by a plasma membrane, inside it is the cytoplasm, the organelles that will allow it to carry out its functions and the nucleus, which contains the genetic material. The number and arrangement of the organelles will vary depending on the type of cell. Cell Membrane Plasma Membrane Cell membrane (Animal eukaryotic cells) It is a permeable and selective barrier that separates the external environment from the inside of the cell. In addition to delimiting the cell, it maintains its integrity, regulates interactions with other cells, controls the movement of substances from the interior to the exterior or vice versa, recognizes molecules and other cells, maintains a different potential between the inside and the outside of the cell, transduces physical or chemical signals from the external environment in intracellular events. Components: The cell membrane consists mainly of lipids and proteins that can be of different types: Phospholipids • Lipids (40-50%): Glycolipids Cholesterol (sterol) Intrinsic (~70%): • Proteins (60-50%): Integral or transmembrane Extrinsic (~30%): Peripheral Phosphoglycerides Phospholipids Nitrogenous compound Phosphate bridge Glycerol Hydrophilic head (polar) Serine → phosphatidylserine Choline → phosphatidylcholine Ethanolamine → phosphatidylethanolamine Inositol → phosphatidylinositol Sphingomyelin Choline Phosphate bridge Hydrophilic head (polar) Sphingosine Saturated FA Hydrophobic tail (non polar) Hydrophobic tail (non polar) rotation flexion Unsaturated FA Phospholipids are the most abundant lipids in the membrane. The phospholipid molecule consists of a polar head (hydrophilic) and two apolar (hydrophobic) tails formed by fatty acids. These phospholipids will form a double layer with the apolar tails inside the membrane and thus leave the polar heads on the surface of the membrane. The tails of fatty acids will remain joined to each other by weak non-covalent bonds, which will allow movements of these molecules and will give flexibility to the membrane while maintaining its integrity. Of the two fatty acids that make up each molecule of phospholipid, one of them is usually unsaturated. The more unsaturated molecules there are, the more fluid the membrane will be. Glycolipids Cholesterol 26 CH3 27 CH CH3 24 CH2 23 CH2 22 CH2 20 21 CH CH3 25 Glucids (sugars) Lateral chain Hydrophilic head (polar) 18 11 Hydrophobic tail (non polar) 19 1 2 3 A 4 CH3 10 5 12 C 9 B 6 8 7 CH3 13 14 17 D 16 15 Steroid Nucleus OH Polar Group In the plasma membrane there are also other lipid molecules with a polar part and a nonpolar part in a lower proportion than the phospholipids that are glycolipids and cholesterol. The glycolipids have two tails of fatty acids linked to a carbohydrate and are located in the membrane between the phospholipids in the same arrangement as these. Cholesterol is located in the spaces between unsaturated tails and it is limiting the ability of movement, but at the same time prevents strong bonds between fatty acids being established, providing fluidity to the bilayer. Membrane proteins The proteins that are part of the membrane can be integrated into the membrane, (integral or intrinsic proteins), or they can be associated with the membrane, generally by its cytosolic side (extrinsic or peripheral). Most intrinsic proteins (but not all of them) completely cross the membrane and therefore are also called transmembrane. • Intrinsic (~70%): – Integral ▪ Extrinsics (~30%): – Peripheral: • Attached to lipids • Attached to proteins FUNCTION of MB proteins Lipids form the main structure of the membrane, but proteins are also part of the structure of the membrane. And they will also be responsible for many functions of the membrane: Transport: can join molecules to take them from one side of the membrane to the other or they can also form channels that open up to certain stimuli. Union: They can establish cell junctions with other cells or with the medium and can also fix internal structures of the cell itself. Signal reception: the cells need to receive information from the medium and from other cells in order to coordinate within the multicellular organism. Enzymes: catalyze reactions in the vicinity of the membrane. Structure: Fluid Mosaic The proteins and phospholipids form the stable external structure of the cell. The integral proteins float between the phospholipids and that is why this organization of the membrane is known as the fluid mosaic model. Although these proteins often have limited mobility. T T Protoplasm T TT T T T T TT TT T T TT TT T T The protoplasm is the living substance of the cell and is divided into two compartments: - Cytoplasm: extends from the plasma membrane to the nuclear envelope. It is composed mainly of water, where we will find numerous organic and inorganic chemical substances dispersed. This liquid part of the cytoplasm is what we call cytosol. In addition to the cytosol, in the cytoplasm we will find the organelles and the cytoskeleton. - Carioplasm: material that forms the content of the nucleus. Cell organelles Cell organelles RIBOSOMES 25-30nm Minor subunit Major subunit Ribosomes are small organelles made of rRNA that are responsible for protein synthesis. Each ribosome is formed by a major subunit and a minor subunit. The minor subunit has a binding site for the mRNA and another binding site for the tRNA. The mRNA will bind to the ribosome, which will read the information contained in that mRNA chain. The tRNA will add the corresponding amino acid that indicates the mRNA and as the ribosome goes reading the mRNA chain, amino acids will be added to form a protein. We can find ribosomes isolated in the cytosol or associated with membranes. Ribosome localization Associated with membranes When ribosomes are associated with membranes, the proteins they synthesize may be destined to be part of the membranes or may be released outside the cell. POLYSOMES ARNmm Ribosomes that appear isolated in the cytosol, usually associate in groups through a chain of mRNA to synthesize proteins and thus form what we call polyribosomes or polysomes. In this case, the proteins synthesized in the cytosol will be destined to the cell itself. FUNCTION: Protein synthesis Number of ribosomes that form a polysome varies according to the molecular weight of the protein. methionine EPA Endomembrane System ORIGIN: INVAGINATION OF THE PLASMA MEMBRANE: similar structure and composition ENDOPLASMIC RETICULUM GOLGI APPARATUS NUCLEAR ENVELOPE ENDOPLASMIC RETICULUM It is the largest membranous system in the cell. It is a system of tubules and vesicles whose lumen is called cistern. In it we distinguish two different regions that are the Smooth Endoplasmic Reticulum (SER) and the Rough Endoplasmic Reticulum (RER). ROUGH ENDOPLASMIC RETICULUM It is continuous with the nuclear membrane and is formed by a system of elongated cisterns. On its membrane it has associated ribosomes that give it the rough appearance. 30% lipids 70% proteins Function of the RER: participates in protein synthesis. Proteins that are formed in the RER can remain in the RER membrane and be part of this organelle, or they can become part of the plasma membrane. Other proteins synthesized in the RER membrane will be stored inside their cisterns and then they will undergo processing. They will come out through vesicles and go to other organelles or outside the cell. SMOOTH ENDOPLASMIC RETICULUM It is located after the RER and is formed by a network of anastomosed tubes. It does not have ribosomes associated on its membrane. Its main functions are lipids synthesis (steroids, cholesterol, triglycerides) and storage of calcium. GOLGI APPARATUS It consists of one or several series of stacked cisterns that do not completely come into contact with each other. The periphery of each cistern is dilated and surrounded by vesicles in the process of fusing or detaching from this organelle. In each Golgi apparatus, the face closest to the RER and the nucleus is called the cis face. Vesicles from the RER will enter through cis face. The opposite side, of concave shape and oriented towards the plasmatic membrane, is called trans face. This is the exit face of the vesicles. 1898 - Camilo Golgi 4 – 40 Cisterns = Dictiosome Morphological polarity Trans face or maturing: Exit of the dictiosome Cis face or formation: Entrance to the dictiosome Golgi ap. composition: 65% proteins 35% lipids Transport control and direction The proteins manufactured and modified in the RER will come out in vesicles and will be directed mostly to the Golgi apparatus. They enter through the cis face and they will suffer processing and packaging inside of it. Then they will go out through the trans face to go to their final destination. LYSOSOMES It is an organelle of more or less spherical shaped, surrounded by a membrane and full of enzymes of the acid hydrolases type. These enzymes are responsible for degrading different types of molecules and to function they need an acid pH. In the lysosome membrane there are proton pumps that maintain a pH of about 5 in their interior. These enzymes must be surrounded by this membrane precisely to maintain the pH suitable for its operation, but also to avoid damaging other structures of the cell . Inside the lysosome, macromolecules, phagocytosed microorganisms, cell debris or aged organelles are degraded. All the degraded material can be reused by the cell, or it is expelled to the outside. Lysosomal vesicles: lysosomes 1º Lysosomes are formed as vesicles coming out of the Golgi apparatus. They are released at the trans face with the enzymes inside. Subsequently, these vesicles fuse with other lysosomes or with vesicles of endocytosis and thus pour their enzymes into that other vesicle to begin the digestion of their contents. clathrin Fusion with existing lysosomes 1 or 2 Golgi (trans face) PRIMARY LYSOSOME: the one that has never intervened in catabolic processes, that is, the vesicle formed in the Golgi. SECONDARY LYSOSOME: the one that has already participated in catabolic processes. TERTIARY LYSOSME (or residual body): it's a lysosome that contains compounds resistant to complete digestion and remain stored in it. PEROXISOMES They are organelles also surrounded by membrane, spherical or oval in shape, which contain oxidative enzymes. They intervene in the degradation of fatty acids, where hydrogen peroxide (H2O2) is obtained. H2O2 is a very reactive substance that degrades some toxic agents and microorganisms, but it can also damage structures of the cell itself, that is why it is used inside this organelle. MITOCHONDRIA They are flexible organelles in the shape of a cane. Inside them, oxidative phosphorylation is performed to obtain ATP. ATP is a stable molecule that stores energy. Mitochondria are the organelles responsible for using oxygen from the air (cellular respiration) and glucose to obtain energy for the cells to carry out their functions. Mitochondrias have a smooth outer membrane and another inner membrane with numerous folds that we call cristae that greatly increase the surface of this membrane. The outer membrane is quite permeable to small molecules and therefore the content of the space between the two membranes is very similar to that of the cytosol. In the inner membrane there are protein complexes that form the ATP synthase and the electron transport chain, both responsible for the generation of ATP. Inside the internal membrane there is a dense liquid that we call matrix. The matrix contains the enzymes of the Krebs cycle, which is the previous step to the electron transport chain to obtain ATP. Mitochondrial DNA Ribosomes In the mitochondrial matrix we will also find some ribosomes that will be responsible for the synthesis of mitochondrial proteins. In addition, there is also DNA that contains genetic information of the mitochondria, but this DNA has nothing to do with nuclear DNA. It is a much simpler DNA, circular and unpacked, much more similar to prokaryotic organisms. That is why there is a theory that says mitochondria were prokaryotes that began to live in symbiosis with eukaryotic cells. In addition, mitochondria are also self-replicating organelles, they are able to duplicate their DNA content and divide by fission. Interphase Nucleus NUCLEUS. General features It is the largest organelle in the cell and is responsible for storing the genetic material. It contains most of the cell's DNA and the mechanisms for the synthesis of RNA and for the assembly of ribosomes. It is usually located in the center of the cell and is spherical, but depending on the function of the cell, its cytoplasmic content or its shape, the nucleus can vary its position, shape and size. Most cells have a single nucleus, but in humans we can find some cells with several nuclei such as osteoclasts, and others that have lost it such as erythrocytes. COMPONENTS External nuclear mb • Nuclear envelope – External nuclear membrane Nucleoplasm – Inner nuclear membrane – Nuclear pores • Nucleoplasm RER – Chromatin – Nucleolus Cytoplasm Inner nuclear mb The nucleus is surrounded by the nuclear envelope, which consists of two concentric parallel membranes separated from each other by a small space called cistern. In certain regions, both membranes fuse together to form nuclear pores, which allow the nucleus to communicate with the cytoplasm. Nucleoplasm. Chromatin The nucleoplasm is the liquid part of the material that fills the nucleus. It has a composition similar to that of the cytosol and it contains the genetic material and the nucleolus. Chromatin is the complex that forms DNA with proteins (mainly histones) for storage. It is the way in which DNA appears when the cell is not in division, that is, in an interphase. Depending on its activity, it can appear in the shape of heterochromatin or euchromatin. Chromatin organization Genetic material packaging Location Activity Euchromatin Loose Nucleoplasm Intense Heterochromatin Packed Lumps Limited Chromosomes When the cell is going to divide, the DNA content doubles, the chromatin fibers condense and the chromosomes appear visible under an optical microscope. The number of chromosomes that appear is specific to each species: ▪ Human: 46 chromosomes (23 pairs of homologous chromosomes) ▪ One chromosome of each pair is inherited from the father and the other from the mother ▪ 22 autosomal chromosomes and 1 sex chromosome (X or Y) ▪ Cells with the complete complement of chromosomes: diploid (2n) ▪ Cells with only one of each pair of homologs: haploid (n) Chromosomes structure armto Brazo Long arm largo BraShort zo cor (q) (p) Sister chromatids Cromátidas hermanas Centrómero Centromere Kinetochore Each identical copy of the DNA will form a chromatid, and two chromatids will join at a point called the centromere to form the chromosome. In the centromere there is a structure called kinetochore, which is where the microtubules of the mitotic spindle will bind during cell division. Cytoskeleton Cytoskeleton: It is a system of tubules and protein filaments that will be responsible for maintaining the shape of the cell, cell movements, the location of the organelles and their movement, stabilize cell junctions, muscle contraction and cell division. The cytoskeleton is made up of three components: Microfilaments (non muscular cells) • Microfilaments Movement Myofilaments (muscular cells) • Intermediate filaments Structure • Microtubules Shape, intracellular transport, cell division MICROFILAMENTS (Actin) OPTICAL MICROSCOPY IMMUNOFLUORESCENCE Bundles 7 nm Networks Microfilaments are formed by a protein called actin that is organized in two chains forming an helix. These actin filaments are grouped forming networks or bundles. The actin networks are located next to the plasma membrane and form the structural basis of the cellular cortex. Bundles of actin can be contractile or non-contractile. In muscle cells there are actin filaments that are organized in a particular way and will be responsible for muscle contraction. Microfilaments (non muscular cells): Contractile bundles are usually associated with another protein, myosin, which moves the actin filaments. They are responsible for the movement of organelles and vesicles, the formation of pseudopods and the formation of contractile rings for cell division. Non-contractile bundles form bundles of closely packed parallel filaments. They form structures such as microvilli. Non contractile bundles Contractile bundles Actin Myosin II Tropomyosin Actinin α Minimyosin Fimbrin Plasma mb Microvilli They are cellular membrane protrusions that have dense bundles of cross-linked actin filaments. The actin filaments here form parallel and rigid bundles. Therefore, these structures increase the surface area of the cell so that it has more contact with the environment. INTERMEDIATE FILAMENTS They have an intermediate diameter between microfilaments and microtubules. They are formed by different types of proteins that share morphological and structural characteristics. They support the cell maintaining its three-dimensional structure. They also support the nucleus and anchor the cytoskeleton to the membrane. 10 nm MICROTUBULES They are hollow cylinders that are organized from a region near the nucleus called centrosome. Each microtubule consists of 13 protofilaments, which are made up of α- and β- tubulin dimers. They are dynamic structures that are continuously stabilizing or depolymerizing, thus suffering changes in length depending on the needs of the cell. They provide rigidity and maintain the shape of the cell, regulate the intracellular movement of organelles and vesicles, intervene in cell division, allow the movement of cilia and flagella. Centroso me 25 nm 1. Complex grouping of microtubules: CENTRIOLE The centrioles are cylindrical structures composed of 9 triplets of microtubules. In animal cells centrioles usually reside in pairs with the cylindrical centrioles at right angles to each other. CENTRIOLES: A pair of centrioles is surrounded by a dense matrix called Pericentriolar material (PCM) and this whole set will form the centrosome (or microtubule organizing center). Microtubules polymerize and depolymerize from the centrosome. Centrosome = Pair of centrioles (Diplosome) + PCM Centriole Pair of centrioles (Diplosome) Location: KINETOCENTER In the proximity of the Golgi next to the nucleus Pericentriolar Material (PCM) Duplication of a centriole from another centriole When a cell goes into division, the centrioles duplicate, each forming a new (daughter) centriole perpendicular to the older (mother) centriole. The two pairs of centrioles will be responsible for forming the mitotic spindle necessary for cell division. The mitotic spindle is also formed by microtubules. 2. Complex grouping of microtubules: CILIA They are extensions of the cell membrane with a microtubule cytoskeleton. Its main structure is formed by a central pair of microtubules surrounded by 9 doublets., The basal body is found at the base of the cilium and is formed by 9 triplets of microtubules. Cilia cover the surface of the cell and move substances from the medium. 2 92+2 MP 92+0 Basal body 93+0 3. Complex grouping of microtubules: FLAGELA The only human cell that has a flagellum is the sperm. Its main structure is the same as that of the axonemes (92 + 2). In the main piece of the tail of the sperm, this structure is surrounded by 9 dense fibers and in the middle part, there is also a sheath of mitochondria that will provide energy for movement. Unlike cilia, each cell has a single, much larger and longer flagellum that serves to move the cell itself. 2 9