VMU_lecture 4_Cell Biology_2024pdfVMU 4 Cell Biology 2024 (1).pdf

Life Sciences I Cell Biology VF/AF/VM-U32 GENERAL PROPERTIES OF BIOLOGICAL MEMBRANES. MATERIAL TRANSPORT THROUGH THE MEMBRANES. CELL SIGNALING. THE CELL CYTOSKELETON. CYTOPLASM AND ITS PROPERTIES. www.lsmu.lt ...

Life Sciences I Cell Biology VF/AF/VM-U32 GENERAL PROPERTIES OF BIOLOGICAL MEMBRANES. MATERIAL TRANSPORT THROUGH THE MEMBRANES. CELL SIGNALING. THE CELL CYTOSKELETON. CYTOPLASM AND ITS PROPERTIES. www.lsmu.lt  Cellular Components Eukaryotic cells have three major components: 1. Cell membranes separate a cell from its environment and form distinct functional compartments (nucleus, organelles) in the cell. The outer cell membrane is called the plasma membrane, or plasmalemma. 2. The cytoplasm surrounds the nucleus and is enclosed by the plasma membrane. It contains the structures and substances that decode the instructions of DNA and carry on the cell's activities. 3. The membrane-limited nucleus contains the DNA, which carries the genetic code for protein synthesis and thus for all cell activities. It also has components that determine which parts of the genetic code are used and that deliver coded information to the cytoplasm. 2  Cell Membranes. General properties of biological membranes. Material transport through the membranes. 3  The plasma membrane, also called the cell membrane, is the membrane found in all cells that separates the interior of the cell from the outside environment. In bacterial and plant cells, a cell wall is attached to the plasma membrane on its outside surface. 4  Biochemical Components Lipids 1. Lipids in cell membranes include phospholipids, sphingolipids, and cholesterol. ▪ Phospholipids (e.g., lecithin) are the most abundant form. ▪ Each phospholipid molecule has a polar (hydrophilic), phosphate-containing head group and a nonpolar (hydrophobic) pair of fatty acid tails. ▪ Membrane phospholipids are arranged in a bilayer, with their tails directed toward one another at the center of the membrane. 5 http://www.tutorvista.com/content/biology/biology-iii/biomembranes/biomembranes.php# 6 Lipids in membrane structure. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 7 Copyright © 2020 McGraw-Hill Education. All rights reserved Schematic diagram of the biochemical components of plasma membranes (II.A). Labeled components include cholesterol (A), the oligosaccharide moiety (B) of a glycoprotein on the extracellular surface, integral proteins (C and D), phospholipid molecules (E) with their fatty acid tails (F) and polar head groups (G), and peripheral protein (H). Citation: Chapter 2. The Plasma Membrane & Cytoplasm, Paulsen DF. Histology & Cell Biology: Examination & Board Review, 5e; 2010. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=563&sectionid=42045295 Accessed: July 08, 2020 8 Copyright © 2020 McGraw-Hill Education. All rights reserved  Biochemical Components Proteins Proteins may contribute more than 50% of membrane weight. Most membrane proteins are globular and belong to one of two groups: Integral membrane proteins are tightly lodged in the lipid bilayer; detergents are required to extract them. ✓ They are folded, with hydrophilic amino acids in contact with the membrane phospholipids’ phosphate groups and hydrophobic amino acids in contact with the fatty acid tails. Some protrude from only one membrane surface. Others, called transmembrane proteins, penetrate the entire membrane and protrude from both sides. ✓ Some transmembrane proteins, such as protein-3-tetramer, are hydrophilic channels for the passage of water and water-soluble materials through hydrophobic regions. ✓ Some transmembrane proteins pass multiple times through the bilayer to form channels and receptors. ✓ Cryofracture preparations often split plasma membranes through the hydrophobic region, between the ends of the phospholipids’ fatty acid tails. ✓ Most integral proteins exposed in this way remain in the side closest to the cytoplasm, termed the P (protoplasmic) face. The membrane half nearest to the environment, the E (ectoplasmic) face, usually appears smoother. 9  Peripheral membrane proteins are ionically associated with the inner or outer membrane surface and are released in high-salt solutions; some are globular, some filamentous. In erythrocytes, examples on the cytoplasmic surface include adapter proteins like spectrin, which helps maintain membrane integrity, and ankyrin, which links spectrin to protein-3-tetramer. Proteins associated with the membrane lipid bilayer. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 10 Copyright © 2020 McGraw-Hill Education. All rights reserved Membrane proteins. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 11 Copyright © 2020 McGraw-Hill Education. All rights reserved Experiment demonstrating the fluidity of membrane proteins. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 12 Copyright © 2020 McGraw-Hill Education. All rights reserved  Biochemical Components Carbohydrates Carbohydrates occur on plasma membranes mainly as oligosaccharide moieties of glycoproteins and glycolipids. Membrane oligosaccharides have a characteristic branching structure and project from the cell's outer surface, forming a surface coat called the glycocalyx that participates in cell adhesion and recognition. 13 http://www.tutorvista.com/content/biology/biology-iii/biomembranes/biomembranes.php#  Type Description Examples Span the membrane and have a hydrophilic cytosolic domain, which interacts with internal molecules, a hydrophobic Ion Integral membrane-spanning domain that anchors it within the cell channels, proto proteins membrane, and a hydrophilic extracellular domain that n pumps, G or transmembrane interacts with external molecules. The hydrophobic domain protein-coupled proteins consists of one, multiple, or a combination of α-helices and β receptor sheet protein motifs. Covalently bound to single or multiple lipid molecules; Lipid anchored hydrophobically insert into the cell membrane and anchor the G proteins proteins protein. The protein itself is not in contact with the membrane. Attached to integral membrane proteins, or associated with peripheral regions of the lipid bilayer. These proteins tend to Some Peripheral have only temporary interactions with biological membranes, enzymes, som proteins and once reacted, the molecule dissociates to carry on its e hormones work in the cytoplasm. 14  Membrane Organization The fluid mosaic model describes biologic membranes as “protein icebergs in a lipid sea”. Integral proteins exhibit lateral mobility and may rearrange through their association with peripheral proteins, cytoskeletal filaments within the cell, membrane components of adjacent cells, and extracellular matrix components. Integral proteins may diffuse to and accumulate in one membrane region. Membrane asymmetry refers to differences in chemical composition between the bilayer's inner and outer halves. Oligosaccharides occur only on the plasma membrane's outer surface. Phospholipid asymmetries also occur. The outer half has more phosphatidyl choline and sphingomyelin and the inner half has more phosphatidyl serine and phosphatidyl ethanolamine. 15 16  MEMBRANE FUNCTIONS 1. Selective permeability. Cell membranes separate the internal and external environments of a cell or organelle, preventing the intrusion of harmful substances, the dispersion of macromolecules, and the dilution of enzymes and substrates. This selective permeability is essential for maintaining the functional steady state, or homeostasis, required for cell survival. Homeostatic mechanisms attributable to cell membranes maintain optimal intracellular concentrations of ions, water, enzymes, and substrates. Three mechanisms allow selected molecules to cross membranes. 17 Major mechanisms by which molecules cross membranes. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 18 Copyright © 2020 McGraw-Hill Education. All rights reserved a. Passive diffusion Some substances (e.g., water and lipids) can cross the membrane in either direction following a concentration gradient, without the cell expending energy. 19 b. Facilitated diffusion Some molecules (e.g., glucose) are helped across the membrane by a membrane component. This facilitated diffusion is often unidirectional, but it follows a concentration gradient and requires no energy. 20  c. Active transport Some molecules enter or exit a cell against a gradient. This requires energy, usually as adenosine triphosphate (ATP). One active transport mechanism is the sodium pump (Na+/K+-ATPase), which expels sodium ions from a cell even when the sodium concentration is higher outside than inside. 21 https://factfile.org/wp-content/uploads/2014/11/Active-Transport-Pictures.jpg  22 https://www.youtube.com/watch?v=ufCiGz75DAk 2. Signal transduction. Integral membrane receptor proteins with strong binding affinities for signal molecules (e.g., neurotransmitters, peptide hormones, and growth factors) are found on cell surfaces. The signal molecule to which a receptor specifically binds is its ligand. The receptor transduces the signal across the membrane without the ligand entering the cell. These receptors are critical to intercellular communication. Signal transmission depends on the receptor class involved. There are receptor classes. a. Ligand-gated (e.g., transmitter-gated) ion channels are long proteins that pass multiple times through the plasma membrane. b. Enzyme-linked receptors comprise a heterogeneous group of transmembrane (typically single-pass) proteins associated with an enzyme (typically a protein kinase) or possessing kinase activity of their own (e.g., tyrosine kinase). c. G protein–coupled receptors (GPCRs) comprise a family of proteins that make seven passes through the membrane. d. Steroid hormone receptor family. 23 Major types of membrane receptors. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 24 Copyright © 2020 McGraw-Hill Education. All rights reserved Schematic diagrams of signal-transducing membrane receptors. A. Ion channel–linked receptor (transmitter-gated ion channel). Ligand binding causes a conformational change in the receptor, allowing ions to pass through the membrane. B. Enzyme-linked receptor. Ligand binding causes a conformational change in the receptor that activates an enzyme (e.g., kinase) that is part of the receptor (shown) or another protein associated with the cytoplasmic domain of the receptor (not shown). Citation: Chapter 2. The Plasma Membrane & Cytoplasm, Paulsen DF. Histology & Cell Biology: Examination & Board Review, 5e; 2010. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=563&sectionid=42045295 Accessed: July 08, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved 25  3. Endocytosis. Cells engulf extracellular substances and bring them into the cytoplasm in membrane-limited vesicles by mechanisms described collectively as endocytosis. The different types of endocytosis 26 https://en.wikipedia.org/wiki/Endocytosis a. In phagocytosis (cell eating), the cell engulfs insoluble substances, such as large macromolecules or entire bacteria. The vesicles formed are termed phagosomes. b. In pinocytosis (cell drinking), the cell engulfs small amounts of fluid, which may contain a variety of solutes. Pinocytotic vesicles are smaller than phagosomes. 27  c. In receptor-mediated endocytosis, a cell engulfs ligands along with their surface receptors. The binding of ligand to receptor causes the ligand–receptor complexes to collect in a coated pit, a shallow membrane depression whose cytoplasmic surface is covered with the coat protein, clathrin. After further invagination, the protein, dynamin, coils around the neck of the budding vesicle and pinches it off to create a coated vesicle, which carries the ligand–receptor complexes into the cell. The clathrin coat is released from the vesicle, now termed an early endosome, and the ligands dissociate from the receptors. The late endosome, or compartment of uncoupling of receptor and ligand (CURL), becomes more tubular and divides into two portions, segregating the receptors from the ligands. The portion with the receptors pinches off and returns to fuse with the plasma membrane. The portion with the ligands fuses with a lysosome. 28 https://www.sigmaaldrich.com/life-science/metabolomics/enzyme-explorer/learning-center/structural-proteins/clathrin.html Three major forms of endocytosis. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 29 Copyright © 2020 McGraw-Hill Education. All rights reserved Receptor-mediated endocytosis involves regulated membrane trafficking. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 30 Copyright © 2020 McGraw-Hill Education. All rights reserved Schematic diagram of receptor-mediated endocytosis (II.C.3.c). Citation: Chapter 2. The Plasma Membrane & Cytoplasm, Paulsen DF. Histology & Cell Biology: Examination & Board Review, 5e; 2010. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=563&sectionid=42045295 Accessed: July 08, 2020 31 Copyright © 2020 McGraw-Hill Education. All rights reserved 4. Exocytosis ejects substances from the cell. Cells use exocytosis both for secretion and for excretion of undigested material. A membrane- limited vesicle or secretory granule fuses with the plasma membrane and releases its contents into the extracellular space, without disrupting the plasma membrane. 32  33 https://www.youtube.com/watch?v=BGeSDI03aaw  Membrane Functions 5. Compartmentalization. Membranes selectively block the passage of most water-soluble substances. The cytoplasm has many membrane-limited compartments (organelles), each with different internal solute concentrations. This compartmentalization prevents the dilution of substrates, metabolic intermediates and cofactors in multistep biochemical reactions, and protects sensitive reactions from the intrusion of extraneous substances. 34  Membrane Functions 6. Spatial–temporal organization of metabolic processes. Some cell membranes (e.g., inner mitochondrial membrane and Golgi complex) contain enzymes arranged in series so that intermediates in multistep metabolic processes are passed from enzyme to enzyme. This arrangement maintains the chronologic order of such processes and sets rate limits by maintaining local concentrations of intermediates. 7. Storage, transport, and secretion. Substances in vesicles may be kept for later use (storage), shuttled from one compartment to another for further processing (transport), or expelled from the cell (secretion). 35  CYTOPLASM AND ITS PROPERTIES Cytoplasm Cytoplasm is all of the material within a cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The main components of the cytoplasm are cytosol – a gel-like substance, the organelles – the cell's internal sub-structures, and various cytoplasmic inclusions. The cytoplasm is about 80% water and usually colorless. The submicroscopic ground cell substance, or cytoplasmatic matrix which remains after exclusion the cell organelles and particles is groundplasm. It is the hyaloplasm of light microscopy, and high complex, polyphasic system in which all of resolvable cytoplasmic elements of are suspended, including the larger organelles such as the ribosomes, mitochondria, the plant plastids, lipid droplets, and vacuoles. 36  Cytoplasm Most cellular activities take place within the cytoplasm, such as many metabolic pathways including glycolysis, and processes such as cell division. The concentrated inner area is called the endoplasm and the outer layer is called the cell cortex or the ectoplasm. Movement of calcium ions in and out of the cytoplasm is a signaling activity for metabolic processes. In plants, movement of the cytoplasm around vacuoles is known as cytoplasmic streaming. 37  Cytosol The cytosol is a component of cytoplasm. The cytoplasm encompasses all of the material in the cell membrane, including the organelles, but excluding the nucleus. So, the liquid within mitochondria, chloroplasts, and vacuoles is part of the cytoplasm, but is not a component of the cytosol. In prokaryotic cells, the cytoplasm and the cytosol are the same. 38  Cytosol The cytosol consists of a variety of ions, small molecules, and macromolecules in water, however, this fluid is not a homogeneous solution. About 70% of the cytosol is water. In humans, its pH ranges between 7.0 and 7.4. The pH is higher when the cell is growing. Ions dissolved in the cytosol include K+, Na+, Cl-, Mg2+, Ca2+, and bicarbonate. It also contains amino acids, proteins, and molecules that regulate osmolarity, such as protein kinase C and calmodulin. The concentration of substances in the cytosol is affected by gravity, channels in the cell membrane and around organelles that affect calcium, oxygen, and ATP concentration, and channels formed by protein complexes. The cytosol serves several functions within a cell. It is involved in signal transduction between the cell membrane and the nucleus and organelles. It transports metabolites from their production site to other parts of the cell. It is important for cytokinesis, when the cell divides in mitosis. The cytosol plays a role in eukaryote metabolism. 39  THE CELL CYTOSKELETON Cytoskeleton The cytoskeleton, a mesh of filamentous elements called microtubules, microfilaments, and intermediate filaments, provides structural stability for maintaining cell shape. It is also important in cell movement and rearranging cytoplasmic components. 40 http://thebuildingblockofbiology.files.wordpress.com/2013/01/cyto.jpg Microtubules and actin filaments in cytoplasm. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved 41  THE THREE CYTOSKELETAL FILAMENTS 42 https://www.coursehero.com/sg/cell-biology/structure-of-the-cytoskeleton/  Microtubules Structure Microtubules are the thickest (24-nm) cytoskeletal components. The walls consist of subunits called tubulin heterodimers, each of which comprises one α-tubulin and one β-tubulin protein molecule. The tubulin heterodimers are arranged in threadlike chains called protofilaments, 13 of which align parallel to one another to form the wall of each microtubule. 43 micro.magnet.fsu.edu  Microtubules Structure Each microtubule is polarized, with a plus (+) and minus (−) end. They exist in a state of dynamic instability, undergoing abrupt changes in length through changes in the balance between polymerization and depolymerization. Function Microtubules form a network of roadways in the cell, deploy cytoplasmic organelles (including the ER and Golgi complex), shuttle vesicles from one part of the cell to another, and move chromosomes during mitosis. Their instability is critical to their function. 44 http://depositphotos.com/13591868/stock-illustration-Structure-and-assembly-of-microtubules-eps8.html Dynamic instability of microtubules. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 45 Copyright © 2020 McGraw-Hill Education. All rights reserved Schematic diagrams of microtubules and their contributions to cilia and centrioles. A. Microtubules as seen by the electron microscope. Cross-sections of tubules show a ring of 13 subunits of dimers arranged in a spiral. Changes in microtubule length are caused by the addition or loss of individual tubulin subunits. B. A cross-section through a cilium reveals a microtubule complex, or axoneme, at its core. An axoneme consists of two central microtubules surrounded by nine microtubule doublets (9 + 2). In the doublets, the A microtubule is complete and consists of 13 subunits, whereas the B microtubule shares two or three heterodimers with the A. When activated by ATP, the dynein arms (which harbor ATPase) link adjacent tubules and provide for the sliding of doublets past each other. C. Centrioles consist of nine microtubule triplets in a pinwheel array. In the triplets, the A microtubule is complete and consists of 13 subunits, whereas the B and C microtubules share tubulin subunits. These organelles typically occur in pairs disposed at right angles to each other. (Reproduced, Citation: withPlasma Chapter 2. The permission, from Membrane Junqueira & Cytoplasm, LC, Carneiro Paulsen J, Basic DF. Histology & Cell Histology: Text & Atlas, Biology: Examination & Board11th ed.5e; Review, McGraw-Hill, 2010. AvailableInc., at: New York, 2005.) https://accessmedicine.mhmedical.com/content.aspx?bookid=563&sectionid=42045295 Accessed: July 08, 2020 Copyright © 2020 McGraw-Hill Education. All rights reserved 46  Microfilaments Structure Microfilaments are the thinnest cytoskeletal elements (5–7 nm) and are more flexible than microtubules. They are filamentous polymers of one of several types of globular actin protein monomers. In striated muscle cells, actin filaments form a stable paracrystalline array in association with myosin filaments. Actin filaments in other cells are less stable and repeatedly dissociate and reassemble. These changes are regulated in part by calcium ions, cAMP, and by a host of actin-binding proteins in the cytoplasm and attached to the plasma membrane's cytoplasmic surface. In addition to regulating polymerization and depolymerization, actin-binding proteins arrange microfilaments into the networks and bundles that carry out their many important functions. 47 Actin filament treadmilling. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 48 Copyright © 2020 McGraw-Hill Education. All rights reserved Centrosome. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 49 Copyright © 2020 McGraw-Hill Education. All rights reserved Roles of major actin-binding proteins in regulating the organization of microfilaments. Citation: The Cytoplasm, Mescher AL. Junqueira’s Basic Histology: Text and Atlas, 15e; 2018. Available at: https://accessmedicine.mhmedical.com/content.aspx?sectionid=190276157&bookid=2430 Accessed: July 10, 2020 50 Copyright © 2020 McGraw-Hill Education. All rights reserved  Microfilaments Function Microfilaments are contractile, but to contract they must interact with myosin, the only actin-associated motor-protein family. In muscle cells, myosin forms thick filaments. In nonmuscle cells, it exists in soluble form and binds to microfilaments by its globular head, leaving its tail (free end) to attach to the plasma membrane or other cellular components to move them. Each actin monomer harbors an ATP molecule that promotes binding during polymerization but hydrolyzes to ADP shortly after binding to destabilize the microfilament, unless stabilizing actin–binding proteins are present. Location In nonmuscle cells, microfilaments form an irregular cytoplasmic mesh. Local accumulations occur as a thin sheath under the plasma membrane called the terminal web; as parallel strands in cores of microvilli; in the cytoplasm at the leading edge of pseudopods; in association with the plasma membrane, organelles, or other cytoplasmic components; or as a belt around the equator of dividing cells. 51  Intermediate filaments Structure Intermediate filaments are ropelike and composed of shorter threadlike protein subunits twisted around one another to form filaments with a diameter (10–12 nm) intermediate between microtubules and microfilaments. Their protein subunits are globular at their amino and carboxy terminals, with an elongated, linear central domain. The individual proteins belong to the same family as nuclear lamins and differ depending on the cell type. Examples: cytokeratins in epithelial cells, vimentin in mesenchyme derived cells (e.g., fibroblasts, chondrocytes), desmin in muscle cells, glial fibrillary acidic protein in glial cells, and neurofilaments (intermediate filament bundles) in neurons. The stability and longevity of these proteins, together with their cell-type specificity, make them particularly useful in immunohistochemical determination of the origin of neoplastic cells. 52 ps://www.macmillanhighered.com/BrainHoney/Resource/6716/digital_first_content/trunk/test/morris2e/morris2e_ch10_5.html  Intermediate filaments Function Intermediate filaments are notable for their tensile strength and durability. Their abundance in cells subjected to mechanical stress (e.g., cells of skin, connective tissue, and muscle) indicates a role in stabilizing cell structure and in the many functions that depend on maintaining cell shape. Location In most cells, intermediate filaments form a network surrounding the nucleus and extend throughout the cytoplasm. Their ordered arrangement in certain cells (e.g., neurons and keratinocytes of the skin) reflects their special role in maintaining cell shape. 53