5th Week - CellMoleBio PDF

College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City...

College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 Week 4-5: Unit Learning Outcomes (ULO): At the end of the unit, you are expected to a. explain the crucial role of the plasma membrane in the life of the cell. b. describe how the cell changes its behavior in response to environmental stimuli. Big Picture in Focus ULO-b. Describe how the cell changes its behavior in response to environmental stimuli. In this segment, the important terminologies related to the topic denoted in the ULO- b will be operationally and theoretically defined to establish a collective understanding needed for the discussion of the topics. You will encounter these vocabularies as we go through the details of the discussion. Please refer to these definitions when you have difficulty in understanding some concepts. 1. Extracellular Matrix Extracellular Matrix (ECM) is a collection of extracellular molecules secreted by cells that provides structural and biochemical support to the surrounding cells. Common to all eukaryotic cells, particularly the animal cell, release substances into the outside environment of the cellular space. 2. Glycosaminoglycan (GAG) These are repeating disaccharide units which composed of chondroitin sulfate (glucaronate and N-acetyl galectosamine); keratin sulfate (glucaronate and N- acetylglucosamine); and hyaluronate (glucaronate and N-acetylglucosamine). 3. Collagen The most prominent among all proteins that is found in the extracellular matrix is the collagen. Collagen forms into filaments that are intertwined with polysaccharides having proteins which is the proteoglycans. 4. Elastin The kinds of tissues that contain elastin have a greater elasticity than tensile strength such as the arteries, lungs, and intestines. Structurally, the elastins differ from the collagen because it contains glycine, proline and not hydroxylated form that are single molecules are cross-linked via covalent bonds between lysine. 5. Fibronectins Fibronectins are the most common adhesive glycoproteins that belong to the family of glycoproteins. They may be soluble, insoluble or an intermediate form. They are all encoded by same gene, the differences may due to the RNA processing. Structurally, 1|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 they are two (2) polypeptide chains joined by 2 s-s bonds near carboxyl end of molecule; have different domains. 6. De novo synthesis It denotes to the synthesis of large molecules from basic molecules such as polysaccharides from the monosaccharides and proteins from the amino acids. It is an opposite reaction to the recycling after partial degradation 7. Laminins These are adhesive proteoglycans found in basal lamina. The ECM underlying epithelial cells that separates them from connective tissue. 8. Glycocalyx The CHO molecules rich zone in animals’ cells outside of plasma membrane. These molecules are important in cell adhesion, recognition, protection, and creation of permeability barriers. The glycocalyx, which is also referred to as the pericellular matrix of the cell membrane. These molecules are composed of glycoprotein and glycolipid that surround the cell membrane. 9. Cadherins These are molecules named for "calcium-dependent adhesion". One of the types of Cell Adhesion Molecules (CAM) which function for the formation of adherens junction, bind cells with each other. These molecules are highly dependent to the calcium (Ca) ions to function. 10. Plasmodesmata A conduit between the cell walls of two adjacent plant cells. Plasmodesmata allow materials to pass from the cytoplasm of one plant cell to the cytoplasm of an adjacent cell. It is common to all plant cells to have long stretches of the plasma membranes of the adjacent cells for they are separated by the rigid cell wall. In this portion, you will accomplish the Unit Learning Outcomes stipulated in the Big Picture. Your understanding of the following concepts is essential to proceed with successive topics. You may refer to other available references to explore more on the subjects. Thus, you are expected to utilize other books, research articles, and other available resources in the university’s library, e.g., ebrary, search. proquest.com, etc. LECTURE EXTRACELLULAR ENVIRONMENT AND INTERACTIONS Extracellular Matrix Extracellular Matrix (ECM) is a collection of extracellular molecules secreted by cells that provides structural and biochemical support to the surrounding cells. Common to all eukaryotic cells, particularly the animal cell, release substances into the outside environment 2|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 of the cellular space. The principal compositions of the said substances that are released are the proteins. There are various types of proteins due to the different proportion and combination of the amino acids. The most prominent among all proteins that is found in the extracellular matrix is the collagen. Collagen forms into filaments that are intertwined with polysaccharides having proteins which is the proteoglycans. Proteoglycans are the substances which are glycosaminoglycans (GAG) attached to a protein molecule. This is due to the many negative charges which attract water, and cations in large amounts that sucked the water into the matrix. The actions adopt an extended conformation and form gels even at low concentration. What is a glycosaminoglycan? These are repeating disaccharide units; chondroitin sulfate (glucaronate and N-acetyl galectosamine); keratin sulfate (glucaronate and N-acetylglucosamine); and hyaluronate (glucaronate and N-acetylglucosamine). In cartilage, many proteoglycans are attached to hyaluronate to form large complex that give pliability and residence to cartilage. Hyaluronate are glycosaminoglycan (GAG) found in various connective tissues of the humans. They occur unattached to protein that play a role in the joint’s lubrication. During tissues development, they act as a space filler into which the cells of developing tissues can migrate like the formation of heart and cornea. Proteoglycans can also regulate the activities of secreted signaling molecules. They can bind the growth factors that can either enhance or inhibit the signaling activity. Glycosaminoglycans bonded to a protein molecule because of the amount of negative charges that attract water, and the large number of cations tend to imbibed water into the matrix that enable to adopt lengthy conformation and form into gel-liked in low concentration. The core proteins molecules have diverse in size that range from 10,000 to 500,000 molecular weight, number and length of carbohydrate chains vary from 1-200/molecule – 800 monosaccharides long. The term extracellular structures refer to the cell wall, cell membrane and the extracellular matrix. The extracellular structures come from the secretion of the cell that consist of the fibrous proteins, polysaccharides, glycoproteins, and amorphous matrix. Together, these 3|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 materials are structures of the external surface of the cell which is the extracellular matrix. The three types of macromolecules found in the ECM of animal cells are the: a. structural proteins fibers which are the collagens and elastins; b. proteoglycans that serve as the medium, and c. adhesive glycoproteins that attach cells to matrix such as the laminins and fibronectins. The different kinds of molecules, both proteins and proteoglycans, having a ratio of different components could produce different variety of ECM. Hence, the ECM anchor the basic unit of tissue together and also enable the cells to interconnect and communicate with other. Besides providing stability to the physical structure of tissues, the ECM influences the migration and development of cells, cell proliferation, and cell shape. Also, the ECM is usually associated with connective tissue like bone, ligaments, tendons, and cartilage. The figure below depicted the assembly of collagen. Procollagen, a precursor of the collagen that is secreted from cells. Three chains assembled with the action of the collagen peptidase that cleaves the ends to form collagen molecules. Collagen molecules assemble to form fibrils. fibrils assemble into fibers. The Hydrogen bond between OH groups of proline and lysine form to stabilize molecules in fibers. There are different α chains existed that depended on the codes by different genes that form different types of collagen. 4|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 The extracellular matrix consists of a network of proteins and carbohydrates. Other type of protein is the Elastin. The kinds of tissues that contain elastin have a greater elasticity than tensile strength such as the arteries, lungs, and intestines. Structurally, the elastins differ from the collagen because it contains glycine, proline and not hydroxylated form that are single molecules are cross-linked via covalent bonds between lysine. The extracellular matrix also functions as protein receptors which are located on the surface of the plasma membrane. When a particular substance in the extracellular matrix combined with the receptor, it will alter the structural form of the receptor. It will undergo conformation that will position the microfilaments inside the plasma membrane. The said positioning will initiate a chemical signal in the internal environment of the cell that induce the nucleus to turn “on” or “off” it’s activities such as the transcription of DNA. The altered activity of the nucleus will affect the internal cellular activity. 5|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 The common functions of the ECM are the cell adhesion, cell-to-cell communication and cell differentiation. It provides support, segregating tissues from one another, and regulating intercellular communication. It also regulates a cell's dynamic behavior and it sequesters a wide range of cellular growth factors and acts as a local store for them. It performs a De novo synthesis that denotes to the synthesis of large molecules from basic molecules such as polysaccharides from the monosaccharides and proteins from the amino acids. It is an opposite reaction to the recycling after partial degradation Other Functions of Proteoglycans Adhesive glycoproteins and Cell Adhesion Molecule (CAM) These molecules anchor cells to ECM. They may be part of cell membrane or linked to phospholipids. Fibronectins are the most common adhesive glycoproteins that belong to the family of glycoproteins. They may be soluble, insoluble or an intermediate form. They are all encoded by same gene, the differences may due to the RNA processing. Structurally, they are two (2) polypeptide chains joined by 2 s-s bonds near carboxyl end of molecule; have different domains. Some bind molecules in ECM, others to cell-surface receptors. These molecules function to maintains the cell shape. It may also play a role in cancer cells such as if there is no fibronectin, there is also loss of attachment of the cell. The cell migrations during the stage of development can be blocked with antibodies to the fibronectin. In the plasma, the fibronectin promotes blood clotting, it can attach platelets to fibrin in clot formation. 6|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 Laminins are adhesive proteoglycans found in basal lamina. The ECM underlying epithelial cells that separates them from connective tissue. It functions for the structural support and permeability barrier like the kidney filtration. The laminins have 3 polypeptides held together by disulfide bonds. It has several different binding domains like collagen, type IV, heparin, and cell-surface receptors. Glycocalyx are the CHO molecules rich zone in animals’ cells outside of plasma membrane. These molecules are important in cell adhesion, recognition, protection, and creation of permeability barriers. The glycocalyx, which is also referred to as the pericellular matrix of the cell membrane. These molecules are composed of glycoprotein and glycolipid that surround the cell membrane. The substances coat the cell such as the epithelial cell , bacteria and other cells. The glycocalyx serve as the framework for the support. Mostly, the carbohydrate part of the glycolipid located in the plasma membrane function for the cell-to- cell recognition, communication and intercellular adhesion. They also serve as identifier of the cell for recognition such as its own cell and foreign bodies. Highly active in the glycocalyx are the cell-adhesion molecules (CAM) that allow the cells to stick to each other. The molecules direct the movement of cells during embryonic development. Glycocalyx also play important part in the regulation of the vascular tissues such as the volume of the red blood cells in the capillaries. In aquatic species, the slime that protects their external structure are example of the glycocalyx or the polysaccharide matrix covering of the epithelial cells. Cell-Cell Recognition and Adhesion Different Categories of Adhesion Receptors These involves the Immunoglobulin Superfamily (IgSF) proteins like integrins, cadherins, selectins, and. The categories can be characterized as Homophilic interaction , which adhesion occurs when two identical molecules bind, one from each cell and as Heterophilic interaction, which cell adhesion receptor on one cell interacts with different molecule on other cell. All CAMs members of immunoglobulin superfamily contain domains consisting of well-organized loops similar to immunoglobulin subunits. interaction of lymphocytes with cells that mediate immune response; outgrowth and bundling of neurons. 7|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 The kinds of adhesion events the CAMs participate are the interaction of lymphocytes with cells that mediate immune response, the outgrowth , and bundling of neurons. Integrins are transmembrane glycoproteins that bind fibronectins and laminins (fibronectin receptor). These molecules have 2 subunits α and β attached via non-covalent bonds that bind adhesive glycoproteins on outer surface and cytoskeleton element on cytoplasmic surface. They facilitate the cell-to-cell and cell-to-ECM adhesion. These receptors also stimulate signal transduction pathways that facilitate cellular signals like the process of the cell cycle. It also media association of the intracellular cytoskeleton, and the location of the new receptors to the cell membrane. These integrin allow simultaneous responses to all activities at the cell surface such as stimulate the platelets to clot if the condition requires it. Cadherins Cadherins are named for "calcium-dependent adhesion". One of the types of Cell Adhesion Molecules (CAM) which function for the formation of adherens junction, bind cells with each other. These molecules are highly dependent to the calcium (Ca) ions to function. Cell- to- cell adhesion is facilitated by extracellular cadherin domains. In the intracellular cytoplasmic tail that are connected with many adaptors and signaling proteins, generally referred to as the cadherin adhesome. The types of the cadherin are N-cadherin (nervous), E- cadherin (epithelial), P-cadherin (placental). Cadherins are for different tissues. 8|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 Selectins Selectins are carbohydrate binding proteins secreted by cells. These molecules are used to connect cells. Generally, selectins are single-chain transmembrane glycoproteins that characterize by the similarity of properties to C-type lectins due to a related amino tail end and calcium-dependent binding. Selectins bind to polysaccharides and are considered to be a type of lectin. Lectin is a cell adhesion proteins that bind to sugar. There are three subgroups of selectins: a. E-selectin located in the endothelial cells; b. L-selectin found in leukocytes; and c. P-selectin found in platelets and endothelial cells. There is a high connection between red blood cell types and carbohydrate side chains such as Type A have N-acetylgalactosamine at end of CHO attached to membrane glycolipid, Type B have galactose instead, Type AB have both galactose and N-acetylgalactosamin, and Type O – have neither. Cell Connections & Junctions Cell junction is the connection between the adjoining cells or the contact between the cell and extracellular matrix. It is also called membrane junction. Group of cells also interconnect with each other by communication through direct contact. This activity of the cell 9|P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 is referred to as intercellular junctions. There are distinct mechanisms of how plant and animal cells communicate with each other. The intercellular junctions between plant cells are the Plasmodesmata, meanwhile for the animal cell junctions involve the Tight Junctions, Desmosomes, and Gap Junctions. Plant Cell Intercellular Junction: Plasmodesmata A plasmodesmata is a conduit between the cell walls of two adjacent plant cells. Plasmodesmata allow materials to pass from the cytoplasm of one plant cell to the cytoplasm of an adjacent cell. It is common to all plant cells to have long stretches of the plasma membranes of the adjacent cells for they are separated by the rigid cell wall. The transportation of the water, and nutrients from the roots to the different parts of the plant, as well as sugar from the leaves to the other parts of the parts are conducted by the vascular tissues, the xylem and phloem. There is also another mechanism of structural modification of the transport of the substances conducted by the plasmodesmata (plural form)/ plasmodesma (singular form). These are channels that permit the substances from a cell wall to the adjacent plant cells, connected cytoplasm, that enable materials to be transported from cell to cell, and hence, throughout the plant. 10 | P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 Cell junction are classified into three types Occluding junction Communicating junction Anchoring junction. Tight Junctions A tight junction is such a constricted construction that is a watertight seal between two adjacent animal cells. It is very tight that almost impermeable to water except under considerable condition and pressure that alter the structural continuity. The cells are held together very tightly against each other by proteins. There are two most abundant proteins for the tight junctions called claudins and occludins. These proteins generate tight junction adherence. This said tight adherence stops substances from leaking between the cells. These tight junctions are characteristically located in the epithelium that line the internal organs and cavities, and include most of the skin. For instance, the epithelial tissue of the lining of the urinary bladder that prevents urine from leaking out into the extracellular space. Desmosomes Desmosomes are junctions that are also found in the animal cell. These structures act like links between adjacent epithelial cells. The short proteins called cadherins in the plasma membrane attach to the intermediate filaments that assembled to form desmosomes. The cadherins link two adjacent cells together and uphold the cells in a sheet-like formation that make the organs and tissues more elastic, for example the skin, heart, and muscles. Desmosomes produce a very strong linkage structure between cells. It is formed by the connection of cadherins and intermediate filaments. 11 | P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 Gap Junctions The Gap junctions in animal cells can be compared with the plasmodesmata in plant cells. These are channels between adjacent cells which permit the conduct of molecules, and other substances which allow cells to interconnect. These junctions are protein-lined pore that permit water and small molecules to pass between adjacent animal cells. When protein receptors on the surface of the plasma membrane of an animal cell bind to a substance in the extracellular matrix, a chain of reactions begins that changes activities taking place within the cell. Plasmodesmata are channels between adjacent plant cells, while gap junctions are channels between adjacent animal cells. However, their structures are quite different. A tight junction is a watertight seal between two adjacent cells, while a desmosome acts like a spot weld. Gap junctions formed from a set of six proteins which are the connexins in the plasma membrane. They are organized in an elongated donut-like formation called a connexon. When the pores of connexons in adjacent animal cells align, a channel between the two cells forms. Gap junctions are very vital in cardiac muscle which the electrical signal for the muscle to contract is passed efficiently through gap junctions , allowing the heart muscle cells to contract in rhythmically. Hence, animal cells communicate through their extracellular matrices and are interconnected by tight junctions, desmosomes, and gap junctions. Also, plant cells are connected and communicate with each other by plasmodesmata. 12 | P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 You can also refer to the sources below to help you further understand the lesson: Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P., (2015). The Molecular Biology of the Cell (6th Edition) Garland Science, Taylor and Francis Group. Verena lbl, Eva Stoger (2016). Cell Biology and Physiology. New York: Magnum Publishing Marina F. Sanamyan , Julia E. (2016). Cytology, Genetics and cytogenetics. New Rochelle, New York: Magnum Pub. Bruno Pontes,Yareni Ayala (2016). Cell Biology and membrane. New Rochelle, New York: Magnum Pub. Covert, Markus (2015). Fundamentals of systems biology: from synthetic circuits to whole-cell models. Boca Raton :CRC Press,Taylor & Francis Group Mader , Sylvia S. (2016). Biology (12th edition). New York : McGraw-Hill. Mason, Kenneth A. (2017). Biology (11th edition). New York, NY McGraw-Hill Educ. Since you already know the essential concepts in the study of the cell. Let us determine your understanding of the ideas presented in the unit content by answering the following: Identification 1. ____________ - It is the cytoplasmic channels between cell walls. 13 | P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 2. ____________ - They allow small ions and molecules to move from one cell to another membranes , joined by connexons that are hollow cylinders which are made of 6 subunits of connexin that forms hydrophilic channels. 3. ____________ - Give two tissues/organs that have tight junctions. 4. ____________ - 5. ____________ - These are carbohydrate binding proteins secreted by cells that used to connect cells. 6. ____________ - Type of cadherins that are found in the lining of the stomach. 7. ____________ - An interaction of the cell adhesion receptor on one cell interrelates with different molecule on another cell. 8. ____________ - CHO rich zone in animals’ cells outside of plasma membrane. 9. ____________ - Transmembrane glycoproteins that bind fibronectins and laminins. 10. ____________ - Example of tissue that contain elastins. Activity 1. In this activity, you are expected to give a detailed explanation of your answer to the following questions. 1. What leads to the variety of the Extracellular Matrix? _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ 2. What do collagens have in common with skeletal muscle? _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ 3. How are elastins different from collagens? _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ 4. How are proteoglycans related to the structure of cartilage? _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ 14 | P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 5. What effects do cell junctions have on the movement of membrane lipids and proteins? _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ Activity 1. Based on the discussion of the essential concepts and several assessments you have done, what do you think are the three most significant lessons you have learned. Write your answers below. 1. _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ 2. _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ 3. _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ Do you have any questions for clarification? Questions/Issues Answers 1. 15 | P a g e  College of Arts and Sciences Education General Education - Science 2nd Floor, DPT Building, Matina Campus, Davao City Phone No.: (082)300-5456/305-0647 Local 134 2. 3. 4. 5. Extracellular Matrix Signaling Complexes Integrins Cell Adhesion Selectins Collagen Adhesion Molecules Desmosomes Elastin Cadherins Plasmodesmata Glycolipids 16 | P a g e