Cell and Molecular Biology Lecture Notes PDF

Kiya Janua Rini B. Sandoval, M.Sc. MODULE 1.1: INTRODUCTION Cell History Robert Hooke English microscopist Coined the term “cells” in a 1665 publication called Micrographia Observed box-like structures (empty cell walls of dead plant tissue) when he viewed a cork through the lens Cell...

Kiya Janua Rini B. Sandoval, M.Sc. MODULE 1.1: INTRODUCTION Cell History Robert Hooke English microscopist Coined the term “cells” in a 1665 publication called Micrographia Observed box-like structures (empty cell walls of dead plant tissue) when he viewed a cork through the lens Cell History Antonie van Leeuwenhoek A Dutch shopkeeper who had great skills in crafting lenses Observed the movements of protista (a type of single-celled organism) and sperm, which he collectively called “animalcules” Cell History Matthias Schleiden German lawyer turned botanist In 1838, he concluded plants were made of cells and that the plant embryo arose from a single cell Cell History Theodor Schwann German zoologist In 1839, he concluded that the cells of plants and animals are similar structures Proposed two tenets of the cell theory: 1. All organisms are composed of one or more cells. 2. The cell is the structural unit of life. Cell History Matthias Schleiden and Theodor Schwann both agreed that cells could arise from noncellular materials (spontaneous generation or abiogenesis) Rudolf Virchow rejected the theory of spontaneous generation “Omnis cellula e cellula” or “All cells only arise from pre-existing cells” Cell Theory 1. All living things are made up of one or more cells. 2. Cells are the structural and functional unit of life. 3. All cells come from preexisting cells. Cell Diversity Cells exhibit diversity in terms of: Size Shape Internal Organization Cell Size The female egg cell is the largest cell in the human body. Cell Shape The shape and size of the cell depends upon the function they perform. Two Basic Classes of Cells Prokaryotes structurally simpler include Bacteria and Archaea Eukaryotes structurally more complex protists, fungi, plants, and animals Two Basic Classes of Cells Prokaryotes Eukaryotes DNA is not enclosed within a membrane DNA is found in the cell's nucleus, which is and is usually a singular circularly separated from the cytoplasm by a nuclear arranged chromosome membrane, and the DNA is found in multiple chromosomes DNA is not associated with histones DNA is consistently associated with (special chromosomal proteins) histones Lack membrane-enclosed organelles Have a number of membrane-enclosed organelles Their cell walls almost always contain the Their cell walls, when present, are complex polysaccharide peptidoglycan chemically simple Usually divide by binary fission Cell division usually involves mitosis Cell Parts and Function Each cell is surrounded by a membrane and contains parts called cellular organelles. These cellular organelles have specific functions on different parts of a cell: converting energy from nutrients in the food you eat into a form of energy that the cell can use storing the genetic information that serves as the blueprint building the proteins that enable the cell to perform its tasks.  Prokaryotic cells 1. Plasma membrane (or the cell membrane) 1 o a double layer of phospholipids with associated proteins and other molecules o holds all of the intracellular material and regulates the movement of materials into and out of the cell 2. Cytoplasm o gel-like fluid that the cell is filled with o inside the plasma membrane 2 o where all of the cellular organelles are suspended within the plasma membrane 3. Cytoskeletal Proteins o a scaffolding that provides structural support to the cell and is important in cell division o function similarly to the cytoskeleton of Generalized diagram of a bacterial cell. eukaryotic cells Plasma membrane Double layer of phospholipids and proteins Hydrophilic head and hydrophobic tail  Prokaryotic cells 4. Ribosomes o tiny protein-making machines that carry out the genetic instructions of the cell 5 5. Nucleoid o region of the prokaryotic cytoplasm that 4 contains the genome (the main genetic material of the cell and typically have a single, circular chromosome) 6. Plasmids o a non-essential piece of DNA that confers an advantage to the bacteria, such as antibiotic resistance, virulence (the ability to cause disease) and conjugation (a bacterium’s ability to share its plasmids with other bacteria) Generalized diagram of a bacterial cell.  Prokaryotic cells 7 7. Glycocalyx o a layer outside of the cell wall, and present in some bacteria. o There are two types of glycocalyces: a. Slime layers help bacteria stick to things and protect them from drying out, particularly in hypertonic environments. b. Capsules allow bacteria to stick to things, but have the added benefit of helping encapsulated bacteria hide from the host's immune system. Generalized diagram of a bacterial cell.  Prokaryotic cells 8. Cell Extensions o made of delicate protein strands o there are several different types of cell extensions associated with bacteria, including flagella and endoflagella. a. Flagella: These are long whip-like extensions that help bacteria move about the environment. b. Endoflagella (axial filaments): These are 8 also flagella but are wrapped around corkscrew-shaped bacteria and move in waves making the bacteria spin Generalized diagram of a bacterial cell.  Eukaryotic cells: Animal Cell Animal cells and plant cells both have a defined nucleus and other membrane-bound organelles Unlike plant cells, animal cells do not have a cell wall Animal cells are generally smaller than plant cells and come in various sizes and tend to have irregular shapes Animal cells also contain structures such as centrioles, lysosomes, cilia, and flagella that are not typically found in plant cells Generalized diagram of an animal cell.  Eukaryotic cells: Animal Cell 1. Nucleus 1 o Contains all the genetic material in a cell, called DNA o DNA contains all the instructions for making proteins o The nucleus is like the manager’s office of the cell, having individual parts: a. Nuclear envelope: This is a double membrane enclosing the nucleus and is continuous with the endoplasmic reticulum. It is perforated by pores which permit the entry and exit of some molecules.  Eukaryotic cells: Animal Cell 1. Nucleus 1 b. Nucleolus: It is a non-membranous structure involved in the synthesis of ribosomes. It is within the nucleus and the nucleus has one or more nucleoli. c. Chromatin: It is a material consisting of DNA and proteins, and is visible in a dividing cell as individual condensed chromosomes. Eukaryotic cells: Animal Cell 2. Ribosomes o Synthesize all the proteins in the cell, and form the manufacturing 2 department of the cell o It is free in the cell’s cytoplasm or bound to the rough ER or nuclear envelope 3. Endoplasmic Reticulum o A network of flattened, membrane- 3 bound sacs and tubes that are involved in the production, processing, 3 2 and transport of proteins that have been synthesized by ribosomes. o It is like the assembly line of the cell, where the products produced by the ribosomes are processed and assembled.  Eukaryotic cells: Animal Cell o There are two kinds of endoplasmic reticulum: smooth and rough. a. Rough ER : has ribosomes attached to the surface of the sacs and is involved in some protein production, protein folding, quality control and dispatch. b. Smooth ER: does not have RER ribosomes attached and is associated with the synthesis of lipids, steroids, and SER carbohydrates  Eukaryotic cells: Animal Cell 4. Golgi apparatus o Also called the Golgi complex or Golgi body o Receives proteins from the ER and folds, sorts, and packages these proteins into vesicles o It is like the shipping department of the cell o It is an organelle active in synthesis, modification, sorting and secretion of cell products 4  Eukaryotic cells: Animal Cell 5. Lysosomes o Specialized vesicles that contain digestive enzymes o Used extensively within the cell for metabolism and transport of large molecules that cannot cross the membrane unaided o These enzymes can break down large molecules like organelles, carbohydrates, lipids, and proteins into smaller units so that the cell can reuse 5 them o They are like the waste disposal/recycling department of the cell  Eukaryotic cells: Animal Cell 6. Mitochondria o These are the energy-producing organelles, commonly known as “the powerhouse of the cell” o This is where the process of cellular respiration happens o During cell respiration, sugars and fats are broken down through a series of chemical reactions, releasing energy in the form of adenosine triphosphate (ATP) 7. Cytoplasm o The gel-like liquid contained within cells o The cytosol and all the organelles within it, except for the nucleus o Its cytosol consists primarily of water, but also contains ions, proteins, and small molecules, with a pH level of 7 8. Cytoskeleton o A network of filaments and tubules found throughout the cytoplasm of the cell o It gives the cell shape, provides strength, stabilizes tissues, anchors organelles within the cell, and has a role in cell signaling o It also provides mechanical support to allow cells to move and divide o There are three types of cytoskeletal filaments: microfilaments, microtubules, and intermediate filaments 8 7 6  Eukaryotic cells: Animal Cell 9. Cell Membrane o Surrounds the entire cell and separates its components from the outer environment o A double layer made up of phospholipids (called the phospholipid bilayer) and is selectively permeable o Oxygen and carbon dioxide pass through easily, while larger or charged molecules must go through special channels, bind to receptors, or be engulfed 10. Peroxisome o Functions in lipid metabolism and oxidation reactions that produces hydrogen peroxide as a by- product, then converts it to water and oxygen 11. Microvilli o Projections that increase the cell’s surface area 12. Centrosome o The region where the cell’s microtubules are initiated and it contains a pair of centrioles 13. Flagellum o It is the motility structure present in some animal cells, composed of a cluster of microtubules within an extension of the plasma membrane.  13 11 12 9 10 Eukaryotic cells: Plant Cell Differentiated from the animal cells by their cell walls, chloroplasts, and central vacuole Plant cells are more similar in size and are typically rectangular or cube shaped than eukaryotic cells Plant cells are photoautotrophic Turgor pressure in plant cells: created a cell wall pushes against other cell walls due to the expansion of the vacuole While animals rely on a skeleton for structure, turgor pressure in plant cells allows plants to grow tall and reach more sunlight Generalized diagram of a plant cell.  Eukaryotic cells: Plant Cell 1. Chloroplasts o Specialized disk-shaped organelles 1 surrounded by a double membrane o Found only in plants and some types of algae o Carry out the process of photosynthesis a. Stroma: It is a fluid matrix at the center of the chloroplast that is enclosed by the double membrane b. Thylakoids: These are flattened disks within the stroma, and when stacked, is called grana. Thylakoids have a high concentration of chlorophyll and carotenoids, which are pigments that capture light energy from the sun. Generalized diagram of a plant cell. Eukaryotic cells: Plant Cell 2. Vacuoles o a small sphere of plasma membrane within the cell that can contain fluid, ions, and other molecules o the central vacuole of a plant cell helps maintain its turgor pressure 3 3. Cell Wall o A layer found on the outside of the plant cell that gives it strength and also maintains high turgidity 2 o In plants, the cell wall contains mainly cellulose, along with other molecules like hemicellulose, pectin, and lignins, unlike bacterial cell wall which contains peptidoglycan Generalized diagram of a plant cell.  Eukaryotic cells: Plant Cell 3. Cell Wall o It is classified into two: a. Primary cell wall: is a flexible layer formed on 3 the outside of a growing plant cell b. Secondary cell wall: a tough, thick layer formed inside the primary plant cell wall when the cell is mature Generalized diagram of a plant cell. Eukaryotic cells: Plant Cell 4. Plasmodesmata 5 o Cytoplasmic channels through cell walls that connect the cytoplasms of adjacent cells 5. Nucleus o The nucleus contains deoxyribonucleic acid (DNA), the cell’s genetic material, which contains instructions for making 4 proteins o The nucleus also regulates the growth 6 and division of the cell. 6. Ribosomes o Synthesize proteins Generalized diagram of a plant cell. Eukaryotic cells: Plant Cell 7. Endoplasmic Reticulum o Protein modification 8. Golgi Apparatus o The proteins are folded, sorted, and 7 7 packaged into vesicles in this region 9. Mitochondria o These are also found in plant cells 8 o Produce ATP through cellular respiration 9 o Photosynthesis in the chloroplasts provides the nutrients that mitochondria break down for use in cellular respiration Generalized diagram of a plant cell. Eukaryotic cells: Plant Cell 10. Cytoplasm o Contains the organelles, except the nucleus, and the liquid within the cells called the cytosol o the cytosol is mostly made of water, and also contains ions, proteins, and small molecules 11. Cytoskeleton o A network of filaments and tubules found throughout the cytoplasm of the cell o Gives the cell shape, provides 10 strength, stabilizes tissues, anchors organelles within the cell, and has a role in cell signaling. Generalized diagram of a plant cell. Eukaryotic cells: Plant Cell 12. Plasma Membrane o The “bag” that holds all of the intracellular material and regulates 12 the movement of materials into and out of the cell Generalized diagram of a plant cell. MODULE 1.2: BIOCHEMISTRY OF THE CELL TOPICS Water The Nature of Biological Molecules Carbohydrates Lipids Proteins o Primary and Secondary Structures o Tertiary Structure o Quaternary Structure Nucleic Acids  WATER MODULE 1: BIOCHEMISTRY OF THE CELL A. WATER, THE AQUEOUS ENVIRONMENT - biological medium here on Earth - the most abundant substance in living systems, making up 70% or more of the weight of most organisms. - only common substance to exist in the natural environment in all three physical states of matter - According to Henderson: “for life to exist at all, the environment must first be suitable and that leads to water.” 4 EMERGENT PROPERTIES OF WATER 1. Cohesion and Adhesion of Water Molecules 2. Moderation of Temperature by Water. - Water molecules stay close to each other as a result of hydrogen - Water moderates air temperature by absorbing heat from air bonding and these bonds that hold the water together, is a that is warmer and releasing the stored heat to air that is cooler = phenomenon called cohesion. breakage of H-bonds - Adhesion: clinging of one substance to another; counter gravity - heat release (air is cooler)= H-bond formation 3. Evaporative Cooling of Water 4. Water as the Solvent of Life - As a liquid evaporates, the surface of the liquid that remains - Water acts as solvent on a mixture of two or more substances behind cools down. which is called a solution - contributes to the stability of temperature in lakes and ponds - involved in the dissolving of ions which contributes to and also provides a mechanism that prevents terrestrial processes happening in the body such as the formation of the organisms from overheating hydration shell, a sphere of water molecules around each dissolved ion.  Water moving up a plant stem: Water Water droplets on a leaf: The molecules stick together (cohesion) and to water droplets cling together the walls of the xylem vessels (adhesion) to due to cohesion and adhere to move upward. the leaf surface. The Nature of Biological Molecules The bulk of an organism is water. It makes up about 65- 90% of the mass of living organisms1. Once the water evaporates, most of the remaining dry weight is made up of molecules with atoms of carbon It was thought that carbon‐containing molecules were present only in living organisms and thus were referred to as organic molecules to distinguish them from inorganic molecules Biochemicals – compounds produced by living organisms The Nature of Biological Molecules Thechemistry of life centers around the chemistry of the carbon atom Its four outer‐shell electrons allow it to bond with up to four other atoms Each carbon atom can bond with other carbon atoms to construct molecules with backbones containing long chains of carbon atoms The simplest group of organic molecules is the hydrocarbons (contain only carbon and hydrogen)  Functional groups Many of the organic molecules that are important in biology contain chains of carbon atoms, like hydrocarbons, but certain hydrogen atoms are replaced by various functional groups Functional groups – groups of atoms that behave as a unit and give organic molecules their physical properties, chemical reactivity, and solubility in aqueous solution Two of the most common linkages between functional groups are ester bonds, which form between carboxylic acids and alcohols, and amide bonds, which form between carboxylic acids and amines Functional groups Groups with one or more electronegative atoms ( N, P, O, and/or S ) make organic molecules more polar, more water soluble, and more reactive. Classification of Biological Molecules by Function 1. Macromolecules - Huge, highly organized molecules - Contain dozens to millions of carbon atoms - Some perform complex tasks with great precision and accuracy - Four major categories: Proteins, nucleic acids, polysaccharides, and certain lipids Macromolecules Proteins, nucleic acids, and polysaccharides are polymers Polymers are composed of many building blocks or subunits known as monomers Polymerization – the process by which macromolecules are constructed from monomers Where can we find macromolecules in the cell? Classification of Biological Molecules by Function 2. The building blocks of macromolecules - Most of the macromolecules within a cell have a short lifetime compared with the cell itself (except the cell’s DNA) - Macromolecules are continually broken down and replaced by new macromolecules - Hence, most cells contain a supply of precursors of macromolecules - Sugars, which are the precursors of polysaccharides; amino acids, which are the precursors of proteins; nucleotides, which are the precursors of nucleic acids; and fatty acids, which are incorporated into lipids Classification of Biological Molecules by Function 3. Metabolic intermediates (metabolites) - The molecules in a cell have complex chemical structures and must be synthesized in a step‐by‐step sequence beginning with specific starting materials - Metabolic pathway – a series of chemical reactions - The compounds formed along the pathways leading to the end products might have no function per se and are called metabolic intermediates Classification of Biological Molecules by Function 4. Molecules of miscellaneous function - A broad category of molecules but not as large as you might expect; the vast bulk of the dry weight of a cell is made up of macromolecules and their direct precursors - The molecules of miscellaneous function include such substances as vitamins, which function primarily as adjuncts to proteins; certain steroid or amino acid hormones; molecules involved in energy storage, such as ATP; regulatory molecules such as cyclic AMP; and metabolic waste products such as urea Carbohydrates Include simple sugars (or monosaccharides ) and all larger molecules constructed of sugar building blocks Function primarily as stores of chemical energy and as durable building materials for biological construction Most sugars have the general formula (CH2O)n The sugars of importance in cellular metabolism have values of n that range from 3 to 7 3-carbon sugars:trioses, four-carbon sugars:tetroses, five- carbon sugars:pentoses, six-carbon sugares:hexoses, and seven-carbon sugars:heptoses.  Carbohydrates aldose ketose (a,b) Each of the carbon atoms of the backbone is linked to a single hydroxyl group (-OH), except for one that bears a carbonyl (C=O) group. Because of their large numbers of hydroxyl groups, sugars tend to be highly water soluble.  Carbohydrates aldose ketose (c) Sugars having five or more carbons spontaneously self‐react to produce a closed, or ring‐containing, molecule. It is in this form that they are used as building blocks to build other types of carbohydrates.  Carbohydrates aldose ketose The linear form is biochemically important because the aldehyde group at the end of the chain is reactive and can react with proteins, notably hemoglobin. Carbohydrates How are sugars linked? Glycosidic bonds - form by a reaction between carbon atom C1 of one sugar and the hydroxyl group of another sugar, generating a –C- O-C– linkage between the two sugars. Disaccharides Carbohydrates Disaccharides - Molecules with two sugar units - Common function: readily available energy stores - Example: o Sucrose (or table sugar) - a major component of plant sap, which carries chemical energy from one part of the plant to another o Lactose - present in the milk of most mammals; supplies newborn mammals with fuel for early growth and development Carbohydrates Oligosaccharides (oligo=few) - Small chains of sugars - Often found attached to lipids and proteins, converting them into glycolipids and glycoproteins, respectively - Glycolipids and glycoproteins of the plasma membrane - serve to distinguish one type of cell from another and help mediate specific interactions of a cell with its surroundings Carbohydrates Highly branched Polysaccharides - a polymer of sugar units joined by Energy stores glycosidic bonds - Nutritional polysaccharides: glycogen and starch Helical arrangement - Structural polysaccharides: cellulose, chitin, and glycosaminoglycans Glycogen, starch, and cellulose are all made up of glucose subunits, but have very different chemical Energy stores and physical properties due to the distinct ways that Unbranched and highly extended the monomers are linked together. Structural material Lipids a diverse group of nonpolar biological molecules whose common properties are their ability to dissolve in organic solvents and their inability to dissolve in water Lipids of importance in cellular function include fats, steroids, and phospholipids  Fats - a glycerol molecule linked by ester bonds to three fatty acids; the composite molecule is termed a triacylglycerol Fatty acids - long, unbranched hydrocarbon chains with a single carboxyl group at one end - the hydrocarbon chain is hydrophobic, whereas the carboxyl group ( —COOH) is hydrophilic - molecules having both hydrophobic and hydrophilic regions are said to be amphipathic Example: Soaps owe their grease‐dissolving capability to the fact that the hydrophobic end (or nonpolar tails) of each fatty acid can embed itself in the grease, whereas the hydrophilic end (or polar heads) can interact with the surrounding water. As a result, greasy materials are converted into complexes (micelles) that can be dispersed by water. FATTY ACIDS Saturated - Lack double bonds - Densely compacted; solid at room temperature Unsaturated - Possess double bonds - Double bonds produce kinks in a fatty acid chain - Liquid at room temperature - Monounsaturated: only one double bond - Polyunsaturated: more than one double bond Fats Carbohydrates function primarily as a short‐ term, rapidly available energy source, whereas fat reserves store energy on a long‐term basis Fats are extremely insoluble in water and are stored in cells in the form of dry lipid droplets Lipid droplets represent an extremely concentrated storage fuel Adipocytes: - special cells for fat storage - cytoplasm is filled with one or a few large lipid droplets - can change their volume to accommodate varying quantities of fat Steroids - built around a characteristic four‐ringed hydrocarbon skeleton - Cholesterol: a component of animal cell membranes and a precursor for the synthesis of several steroid hormones, such as testosterone, progesterone, and estrogen - Function: chemical messengers - Cholesterol is largely absent from plant cells, which is why vegetable oils are considered “cholesterol‐free” Phospholipids The molecule resembles a fat (triacylglycerol), but has only two fatty acid chains rather than three; it is a diacylglycerol Phospholipids contain two ends that have very different properties Function primarily in cell membranes Proteins Molecular tools and machines that function in many cellular activities Proteins exhibit a high degree of specificity – the shape and surfaces of proteins allow for selective interaction with other molecules Amino acids Building blocks of proteins Each protein has a unique sequence of amino acids Shared properties of amino acids: A carboxyl group and an amino group separated by a single carbon atom (α ‐carbon) Unique property: The side chain or R group Amino acids An amino acid becomes joined to two other amino acids to form a polypeptide chain (a long continuous, unbranched, polymer) Amino acids are joined by peptide bonds (a carboxyl group links to an amino group), accompanied by the elimination of a water molecule Levels of organization of proteins Primary structure - the specific linear sequence of amino acids that constitute the chain - the precise order of amino acids in every protein is determined by the information in the genome - changes that arise in the sequence of a protein due to genetic mutations in the DNA may not be readily tolerated In normal hemoglobin, the amino acid at position six Sickle cells appear crescent-shaped, while normal is glutamate. In sickle cell hemoglobin, glutamate is red blood cells are disc-shaped. replaced by valine.  Levels of organization of proteins Secondary structure: 1. Alpha (α) helix - The backbone lies on the inside of the helix, and the side chains project outward - Held together by hydrogen bonds parallel to the axis 2. Beta (β) sheet - Consists of several segments of polypeptide lying side by side - the backbone of each polypeptide segment assumes a folded or pleated conformation - Hydrogen bonds are oriented perpendicular to the long axis Black = carbon, White = hydrogen, Blue = nitrogen, and Red = oxygen.  Levels of organization of proteins Tertiary structure - stabilized by an array of noncovalent bonds between the diverse side chains of the protein - the tertiary structure determines the interactions and enzymatic activity of a protein - Myoglobin: the first globular protein whose tertiary structure was determined - The first report on the structure of myoglobin revealed that the molecule was compact (globular) and that the polypeptide chain was folded back on itself in a complex arrangement Levels of organization of proteins Tertiary structure - determined by different chemical interactions Levels of organization of proteins Quaternary structure - whereas many proteins such as myoglobin are composed of only one polypeptide chain, most are found in complexes of more than one chain, or subunit - Depending on the protein, the polypeptide chains may be identical or nonidentical - A protein complex composed of two identical subunits is described as a homodimer, whereas a protein complex composed of two nonidentical subunits is a heterodimer Nucleic Acids made from long chains of monomers called nucleotides polynucleotides Primary function: storage and transmission of genetic information Two types: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) Components of a nucleotide: 1. five-membered cyclic monosaccharide Nucleotides = nucleoside + phosphate 2. Nitrogenous base Nucleoside = sugar + base 3. Phosphate group Nitrogenous bases Thymine is present only in DNA molecules Purines Uracil is present only in - six-member ring fused RNA molecules with five-member rings Adenine, guanine, and cytosine are present in both DNA and RNA Pyrimidines - single six-member ring Nitrogenous bases - Cyclic compounds with at least one nitrogen atom in the ring structure - Two types: purines and pyrimidines  5-Carbon sugar Deoxyribose - the 5-carbon sugar in DNA Ribose - the 5-carbon sugar in RNA Difference: Ribose has a hydroxyl group attached to the 2- carbon, while deoxyribose has a hydrogen atom SHORT QUIZ #1 1.Huge, highly organized molecules that contain dozens to millions of carbon atoms 2.Provide the building blocks (or monomers) for each molecule: Carbohydrates Lipids/Fats Proteins Nucleic Acids MODULE 1.3: THE CELL SURFACE AND THE EXTRACELLULAR MATRIX STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX A. Nature and Composition of the Cell Membrane All cellular membranes are selectively permeable (semi-permeable), allowing only certain substances to cross the membrane. All cellular membranes are composed of two layers of phospholipids embedded with proteins and glycoproteins. Different phospholipid and protein compositions give different cellular membranes their unique functions. A.1. The Phospholipid Bilayer Basic phospholipid structure as we understand it today is shown in the space-filling molecular model, highlighting its hydrophilic (polar) head and hydrophobic tails. Molecules with hydrophilic and hydrophobic domains are called AMPHIPATHIC. STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX A. Nature and Composition of the Cell Membrane A.1. The Phospholipid Bilayer When amphipathic molecules are mixed with water they will spontaneously aggregate to ‘hide’ their hydrophobic regions from the water. Phospholipids in water will aggregate so that polar heads face away from each other and the hydrophobic tails interact with each other. STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX A. Nature and Composition of the Cell Membrane A.1. The Phospholipid Bilayer Singer SJ and Nicolson GL (1972) Peripheral proteins: ‘surface proteins’ bind to the surfaces of membranes Integral membrane proteins: span the membrane; mosaic of mobile (fluid) protein ‘tiles’ embedded in a phospholipid medium. a) facilitate the movement of specific molecules in & out of the cell b) adhesion of cells to other cells c) attachment to surfaces d) communication between cells MEMBRANE PROTEINS ARE AMPHIPATHIC AND RESPONSIBLE FOR THE SELECTIVE PERMEABILITY OF MEMBRANES. STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX A. Nature and Composition of the Cell Membrane A.1.1. Chemical Factors Affecting Membrane Fluidity On temperature: higher temperatures result in more molecular motion On fatty acid saturation: unsaturated C-C bonds (especially polyunsaturated fatty acids) have more kinks, or bends On the presence of cholesterol: cholesterol molecules tend to fill the space between fatty acids in the hydrophobic interior of the membrane, reducing the lateral mobility of phospholipid and protein components in the membrane STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX A. Nature and Composition of the Cell Membrane A.1.2. Functional Factors Affecting Membrane Fluidity Examples: 1) Cold-blooded or poikilothermic organisms, from prokaryotes to fish and reptiles, do not regulate their body temperatures. Thus, when exposed to lower temperatures, poikilotherms respond by increasing the unsaturated fatty acid content of their cell membranes; at higher temperatures, they increase membrane saturated fatty acid content. 2) For fish species that range across warmer and colder environments (or that live in climates with changing seasons) membrane composition can change to adjust fluidity. 3) Warm-blooded, homeothermic organisms that maintain a more or less constant body temperature have less need to regulate membrane composition. STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX A. Nature and Composition of the Cell Membrane The plasma membrane is segregated into regions with different properties of fluidity and selective permeability. Extracellular connections between cells as well as intracellular connections of the membrane to differentiated regions of the cytoskeleton effectively compartmentalize the membrane into sub-regions. Just imagine a sheet of epithelial like this one: “Fences and Pickets Model”: proteins attached to the cytoskeleton serve as the pickets. The infrequent movement (hop diffusion) across the fences was infrequent.  STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX B. MEMBRANE PROTEINS Membrane proteins function as: 1) receptors for hormones or neurotransmitters 2) antibodies 3) cell recognition molecules that bind cells together 4) cell-cell communication structures that pass chemical information between cells 5) anchors to extracellular surfaces like connective tissue 6) transporters, allowing the entry into or exit of substances from cells 7) enzymes that catalyze crucial reactions in cells Peripheral proteins - do not penetrate membranes - they bind reversibly to the internal or external surfaces of membranes the biological membrane with which they are associated - serve to regulate the transport or signaling activities of transmembrane protein complexes - may mediate connections between the membrane and cytoskeletal elements STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX Source: Structure of the plasma membrane (article) | Khan Academy STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX B.1. GLYCOPROTEINS AND GLYCOLIPIDS GLYCOPROTEINS glycans (oligosaccharides) covalently linked to amino acids (proteins) enable cell-cell recognition many secreted proteins (e.g., hormones) are also glycoproteins mediate the interaction of cells with extracellular molecular signals and with chemicals of the extracellular matrix GLYCOLIPIDS phospholipids attached to oligosaccharides play a role in cell-cell recognition and the formation of tissues Source: What are glycolipids? Types, properties, and functions - Science Query mediate the interaction of cells with extracellular molecular signals and with chemicals of the extracellular matrix STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MOST COMMON FORMS OF GLYCOPROTEINS N-linked Glycoproteins - N-glycosylation - gain their sugar from the endoplasmic reticulum membrane and then are transported to the Golgi complex for modification - sugar attached to a nitrogen atom of asparagine O-linked Glycoproteins - O-glycosylation - within the Golgi complex - sugar attached to an oxygen atom of serine or threonine - may also bond with hydroxylysine or hydroxyproline STRUCTURES & FUNCTIONS MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MOST COMMON GLYCOLIPIDS Source: 1.4: Glycolipids - Physics Glycoglycerolipids LibreTexts - consists of an acetylated as well as non-acetylated glycerol lipid complex that has at least one fatty acid. - commonly associated with photosynthesizing membranes/tissues of bacteria and plants Glycosphingolipids - based on sphingolipids - major glycolipid in animals, primarily found in the nervous system and are involved in cell signaling. FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT Molecules move in and out of cells in one of 3 ways: a. Passive diffusion - few small, relatively uncharged molecules can cross a membrane unassisted b. Facilitated diffusion - hydrophilic molecules that must enter or leave cells do so with help c. Active transport - molecules are transported against their electrochemical gradients. Passive diffusion and facilitated transport release free energy; active transport consumes it. FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT A. PASSIVE DIFFUSION movement of molecules over time by random motion from regions of higher concentrations to regions of lower concentrations. limited to a few molecules, like gases (O2, CO2, N2) that can freely cross the hydrophobic phospholipid barrier. At equilibrium, solute molecules continue to diffuse across the membrane but for each molecule moving across in one direction, another molecule of the same solute crosses in the other direction. FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT B. FACILITATED DIFFUSION spontaneous (downhill) passage of molecules or ions through specific transmembrane proteins i.e. carrier proteins and channel proteins FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT Carrier proteins allow solute transport B. FACILITATED DIFFUSION specific for a single solute Specific carrier proteins also 😭 facilitate the transport of amino acids and other charged solutes across cell membranes undergo allosteric change when they bind to a solute to be transported AQUAPORINS - assist the movement of water across the cell membrane Aquaporins are required to - allosterically regulated to allow cells to meet their specific water balance facilitate diffusion of water requirements. across membranes at high rates. - others have evolved to cofacilitate the transport of glucose, glycerol, urea, ammonia and carbon dioxide and even ions (protons) along with water. FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT B. FACILITATED DIFFUSION Ion Channels - often formed from more than one integral membrane protein - When stimulated, channel proteins rearrange to open a polar pore to allow specific ion transport. - Some ion channels (like the glucose/sodium ion symport system) mobilize the energy of diffusion to co-transport an ion with another solute through a carrier protein - responsible for the excitability of cells, where Na+ , K+ and Ca++ channels collaborate in ion movements into and out of cells leading to neuronal or muscle cell responses FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT OSMOSIS - water is highly polar and only crosses the hydrophobic phospholipid barrier of cellular membranes very slowly - diffusion of water across membranes from low to high solute concentrations - allows cells to use water to maintain cellular integrity or to adapt to changes in the solute composition of the extracellular environment HYPOTONIC – water enters the cell = SWELL & BURST ISOTONIC – no net movement into or out of the cell HYPERTONIC – water leaves the cell = SHRIVEL UP FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT OSMOTIC PRESSURE AND OSMOREGULATION - changes in osmotic environment can stress or kill an organism e.g. freshwater organisms (protozoa or fish) placed in sea water will die - organisms can osmoregulate, or control the osmotic pressure in their cells, at least to a point. To cope with a constant uptake of water, Paramecium contains contractile vacuoles that collect excess water and then contract to expel the water to maintain water balance (correct osmotic pressure). Freshwater fish cope with their hypotonic environment by urinating a lot Salt-water fish cope with the high solute concentration of solutes (salts) in their environment by excreting excess salt. FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT C. ACTIVE TRANSPORT - there is a difference in charge or potential difference across the membrane: Cells at rest typically have a higher [K+] in the cytosol and higher [Cl-] and [Na+] outside the cell - Membrane depolarization in responsive cells (neuron, muscle) results in a flow of ions, as does the e.g., the ion-assisted symport of glucose - If a substance must move into the cell against its concentration gradient – that is, if the concentration of the substance inside the cell is greater than its concentration in the extracellular fluid (and vice versa), the cell must use ATP - ATP powers active transport is by Active transport mechanisms, transferring a phosphate group collectively called pumps, work against electrochemical gradients. directly to a carrier protein/pumps FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX MEMBRANE TRANSPORT C. ACTIVE TRANSPORT Sodium-potassium Pump exchanges sodium ions for potassium ions across the plasma membrane of animal cells moves two potassium ions into the cell where potassium levels are high, and pumps three sodium ions out of the cell and into the extracellular fluid for every 1 ATP consumed found in the plasma membrane of almost every human cell and is common to all cellular life FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX C. ACTIVE TRANSPORT Sodium-potassium Pump It plays a crucial role on other physiological processes, such as: a. maintenance of filtering waste products in the nephrons (in the kidneys), reabsorb amino acids, reabsorb glucose, regulate electrolyte levels in the blood, and to maintain pH b.sperm motility - regulate membrane potential and ions, which is necessary for sperm motility and the sperm’s acrosome functioning during penetration into the egg c. production of the neuronal action potential - reverse postsynaptic sodium flux to re-establish the potassium and sodium gradients which are necessary to fire action potentials FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX C. ACTIVE TRANSPORT Endocytosis (“inside”) mechanism for internalizing extracellular substances, usually large molecules like proteins, or insoluble particles or microorganisms Three main types: a. Phagocytosis b. Pinocytosis c. Receptor-mediated endocytosis Source: illustration of Healthcare and Medical education drawing chart of Endocytosis cellular process for Science Biology study 2803137 Vector Art at Vecteezy FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX C. ACTIVE TRANSPORT: ENDOCYTOSIS Phagocytosis (“cell eating”) – ‘phago-’ = devouring, ‘-cyte’ = cell – cells in the immune systems of organisms use phagocytosis to devour bodily intruders such as bacteria, and they also engulf and get rid of cell debris – some single-celled organisms like amoeba use phagocytosis in order to eat and acquire nutrients IN THE IMMUNE SYSTEM: Step 1: Activation occurs when the cells are near bacterial cells = receptors Step 2: Immune cells pick up chemical signals and migrate toward invading bacteria or damaged cells Step 3: Cell attaches to the bacterial cell that it will ingest Step 4: The cell ingests the particle, and the bacteria is enclosed in a phagosome that transports the bacteria into the cell Step 5: A lysosome fuses with the phagosome and the bacteria is digested = PHAGOLYSOSOME Source: biology bacteria GIF - Find & Share on GIPHY Step 6: Cellular waste is discharged from the cell = exocytosis FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX C. ACTIVE TRANSPORT: ENDOCYTOSIS Pinocytosis (“cell drinking”) – non-specific, more or less constant pinching off of small vesicles that engulfs extracellular fluid containing solutes; they are too small to include significant particulates – triggered by the presence of certain substances outside the cell such as amino acids or certain ions – it results in the absorption of many different substances by the cell at the same time, such as water and various solutes like sugars and proteins. – e.g. microvilli in the gut use this process to absorb nutrients from food; human egg cells also use it to absorb nutrients prior to being fertilized FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX C. ACTIVE TRANSPORT: ENDOCYTOSIS Receptor-mediated Endocytosis – relies on the affinity of receptors for specific extracellular substances that must be internalized by the cell a. Upon binding their ligands, the receptors aggregate in differentiated regions of cell membrane called coated pits. b. The coated pits then invaginate and pinch off to form a coated vesicle. c. The contents of the coated vesicle are eventually delivered to their cellular destinations, after which their membranes are recycled to the plasma membrane. FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX Source: (265) Pinterest FUNCTIONS AND ACTIVITIES MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX C. ACTIVE TRANSPORT Exocytosis (“exit”) secretion of large molecules such as proteins and glycoproteins like digestive enzymes and many peptide/polypeptide hormones, each of which must exit the cell to either the extracellular fluid or circulation. the endpoint of a complex process of packaging proteins destined to be secreted from the cell or to be membrane proteins themselves necessary to restore plasma membrane internalized by pinocytosis and phagocytosis, and for eliminating cellular waste products. Source: Biology-cell membrane-transport (dynamicscience.com.au) THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX The classes of macromolecules constituting the extracellular matrix in different animal tissues are broadly similar, but variations in the relative amounts of these different classes of molecules and in the ways in which they are organized give rise to an amazing diversity of materials. It has an active and complex role in regulating the behavior of the cells that touch it, inhabit it, or crawl through its meshes, influencing their survival, development, migration, proliferation, shape, and function. THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX The macromolecules that constitute the extracellular matrix are mainly produced locally by cells in the matrix The extracellular matrix is constructed from three major The matrix is an almost infinitely variable materials: classes of macromolecules: Mammals are thought to (1) glycosaminoglycans (GAGs) – large and highly have almost 300 matrix proteins, charged polysaccharides that are usually covalently including about 36 proteoglycans, about 40 collagens, and over 200 linked to protein in the form of proteoglycans glycoproteins! (2) fibrous proteins – primarily members of the An collagen family extracellular (3) a large class of noncollagen glycoproteins – carry matrix is specialized conventional asparagine-linked oligosaccharides for the needs All three classes of macromolecule have many members of that tissue and come in a great variety of shapes and sizes THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX GLYCOSAMINOGLYCANS (GaG) unbranched polysaccharide chains composed of repeating disaccharide units 1st sugar = amino sugar (N-acetylglucosamine or N-acetylgalactosamine), mostly sulfated 2nd sugar = a uronic acid (glucuronic or iduronic) highly negatively charged the most anionic molecules produced by animal cells Four main groups of GAGs (based on their sugars, linkage, and the no. and location of the sulfates): a) hyaluronan b) chondroitin sulfate and dermatan sulfate c) heparan sulfate d) keratan sulfate THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX GLYCOSAMINOGLYCANS (GaG) occupy large amounts of space and form hydrated gels tend to adopt highly extended conformations that occupy a huge volume relative to their mass, and they form hydrated gels even at very low concentrations Their high density of negative charges attracts a cloud of cations (esp. Na+), that are osmotically active = causing large amounts of water to be sucked into the matrix = creates a swelling For example: The cartilage matrix that pressure, or turgor, that enables the matrix to lines the knee joint can support pressures withstand compressive forces of hundreds of atmospheres in this way. THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX GLYCOSAMINOGLYCANS (GaG) Hyaluronic acid can also be injected directly into the joints for pain relief Hyaluronan/Hyaluronic Acid/Hyaluronate simplest of the GAGs Hyaluronic acid serums can reduce found in variable amounts in all tissues and fluids in adult wrinkles, redness, and dermatitis when animals and is especially abundant in early embryos applied on skin surface. FUNCTIONS have a role in resisting compressive forces in tissues and joints. important as a space filler during embryonic development In the developing heart, for example, hyaluronan synthesis helps in this way to drive formation of the valves and septa that separate the heart’s chambers produced in large quantities during wound healing important constituent of joint fluid, in which it serves as a lubricant THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX GLYCOSAMINOGLYCANS (GaG) Proteoglycans Not all proteoglycans are secreted components of the extracellular matrix Some are integral components of plasma membranes and have their core protein either inserted across the lipid bilayer or attached to the lipid bilayer by a glycosylphosphatidylinositol (GPI) anchor THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX FIBROUS PROTEINS Collagen major component of skin and bone most abundant proteins in mammals secreted in large quantities by connective-tissue cells Primary features: a. long, stiff, triple-stranded helical structure, in which three collagen polypeptide chains, called α-chains, are wound around one another in a ropelike superhelix. b. Collagens are extremely rich in proline and glycine, both of which are important in the formation of the triple-stranded helix. THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX FIBROUS PROTEINS Elastin Elastic fibers are at least five times more extensible than a rubber band of the same cross-sectional area Long, inelastic collagen fibrils are interwoven with the elastic fibers to limit the extent of stretching and prevent the tissue from tearing. dominant extracellular matrix protein in arteries narrowing of the aorta and other MARFAN SYNDROME arteries and excessive proliferation of smooth muscle cells in the arterial Caused by mutations in the fibrillin gene wall Fibrillin binds to elastin and is essential for the integrity of elastic fibers THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX FIBROUS PROTEINS Laminin and the Basal Lamina Fibronectin The basal lamina is synthesized by the cells on each side of it: the epithelial cells contribute one set of basal lamina large glycoprotein found in all components, while cells of the underlying bed of connective vertebrates and important for many tissue (called the stroma, Greek for “bedding”) contribute cell– matrix interactions. another set. contribute to both organizing the typically contains the glycoproteins laminin, type IV collagen, matrix and helping cells attach to it and nidogen, along with the proteoglycan perlecan guide cell movements in developing tissues, by serving as tracks along which cells can migrate or as repellents that keep cells out of forbidden areas Mutant mice that are unable to make fibronectin die early in embryogenesis because their endothelial cells fail to form proper blood vessels THE EXTRACELLULAR MATRIX MODULE 1: THE CELL MEMBRANE & EXTRACELLULAR MATRIX Basal Laminae have Diverse Functions In the kidney glomerulus, an unusually thick basal lamina acts as one of the layers of a molecular filter, helping to prevent the passage of macromolecules from the blood into the urine can act as a selective barrier to the movement of cells, as well as a filter for molecules important in tissue regeneration after injury = basal lamina often survives and provides a scaffold along which regenerating cells can Laminin and the Basal Lamina migrate Defects in components of the basal lamina at primary organizer of the sheet the synapse are responsible for some forms of structure, and, early in muscular dystrophy, in which muscles develop development, basal laminae normally but then degenerate later in life. consist mainly of laminin molecules