CMB–Lec(Lesson 1-3).pdf.pdf

Week 1 | Introduction to Cell and For example, In arms, the flat cells (which should be able to protect us from Molecular Biology environmental factors) are in t...

Week 1 | Introduction to Cell and For example, In arms, the flat cells (which should be able to protect us from Molecular Biology environmental factors) are in the _______________________________________ epidermis, in the dermis, there are cuboid cells and spongy cells, and as we proceed Cells and the structures they compromise are to musculoskeletal cells, cruciform cells too small (they should be able to contract and relax) A handful of pioneering scientists had used their are observed handmade microscopes to uncover a world that Neurons – have synapses that transmit would never have been revealed to the naked eye and receive nerve impulses for transfer of I. Robert Hooke (1665) - looked upon slices information and locomotion. of cork C4 Plants can compartmentalize II. Anton van Leeuwenhoek - animalcules, oxygenation and reduction of Theory of Pangenesis, Bovine cells are carbohydrates. round and circular III. Matthias Schleiden/Theodore Schwann Cells Possess a Genetic Program and the - formulated 2 tenets of the Cell theory Means to Use It A. All organisms are composed of Organisms are built according to one or more cells information encoded in a B. The cell is the structural unit of life collection of genes, which are (the basic unit in which it was able constructed of DNA to produce all functions of all The less tolerance of errors in the organisms) nature and interactions of the IV. Rudolf Virchow - third tenet of the cell parts; theory And the more regulation or control A. Cells can arise only by division that must be exerted to maintain from a pre-existing cell the system Cell is the basic unit of life Signal transduction - how the nucleus knows Unlike the parts of a cell, which simply that it’s coming from its environment deteriorate if isolated, whole cells can be Example: Excess/Lacking genetic isolated from an organism and cultured in material (nullisome/trisomy), there are a laboratory where they will grow and higher chances that they are aborted, if reproduce for extended periods. ever born, they have a lower lifespan Death can also be considered one of the Depending on its phenotype, they can also most basic properties of life because only produce maintenance. a living entity faces this prospect. Example: Lactose Operon The first culture of human cells obtained from a malignant tumor from Henrietta Cells Are Capable of Producing More of Lacks was begun by George and Martha Themselves Gey of Johns Hopkins University in 1951 Mitosis/Meiosis To die, one must also be simple to live. Reproduce by division, a process in which the contents of a “mother” cell are Cells are Highly Complex and Organized distributed into two “daughter” cells that The more complex a structure: are genetically identical to their mother The greater the number of parts that must cells be in their proper place; The genetic material is faithfully There is less tolerance for errors in the duplicated, and each daughter cell nature and interactions of the parts; receives a complete and equal share of And the more regulation or control that genetic information must be exerted to maintain the system Cells Acquire and Utilize Energy 1  Light energy is converted by ○ Example: Plants do not have an photosynthesis into chemical energy that immune system but they have is stored in energy-rich carbohydrates, programmed cell death. If there’s a such as sucrose or starch (for pathogen that touches the surface maintenance and also reproduction, and of the leaf, it will try to attack the movement of nutrients to other parts of the adjacent cells of the plant. The cell) plant will kill the adjacent cells For most animal cells, energy arrives found in the opposite direction of prepackaged, often involves form of the the cell. Since the cells are dead, sugar glucose the pathogens can no longer Glucose is disassembled in such way that attach to the dead cells within the its energy content can be stored in a plant. readily available formed called ATP Cells are Capable of Self-Regulation Cell Carry Out a Variety of Chemical Reactions Each type of cellular activity requires a Cells function like miniaturized chemical unique set of highly complex molecular power plants tools and machines - the products of eons All chemical changes that take place in of natural selection and biological cells require enzymes - molecules that evolution greatly increase the rate at which a They can start to evacuate when it comes chemical reaction occurs to the presence of the pests, while doing The sum total of the chemical reaction in a catabolism and anabolism, can do cell cell represents that cell’s metabolism division while multiplying their protein contents if they are expressed. Cells Engage in Mechanical Activities The most fit mutation becomes the norm, Cells are sites of bustling activity for example in photosynthesis, it makes Materials are transported from place to you more compatible in your environment place, structures are assembled and then that is receiving sunlight - Natural rapidly disassembled, and, in any case, Selection. the entire cell moves itself from one site to another Initiated by changes in the shape of “motor” proteins ○ E.g.Cilia for amoeba Cells never stop producing materials. Golgi Apparatus becomes the shipment for the desired products Cells Evolve Changes in cell metabolism that are led by It is presumed that cells evolved from motor proteins. some type of precellular life forms from non-living organic materials that were Cells Are Able to Respond to Stimuli present in the primordial seas. A single celled protist moves away from According to one of the tenets of modern object in its path or moves toward a biology, all living organisms have evolved source of nutrients from a single, common ancestral cell that Most cells are covered with receptors that lived more than three billion years ago interact with substances in the environment in highly specific ways Cells may respond to specific stimuli by altering their metabolic activities, moving from one place to another, or even committing suicide 2  Last universal common ancestor (LUCA) - ○ Such as the production of ATP, term used in… NADPH, and NADH Similar mechanism of photosynthesis ○ Prokaryotes may lack chlorophyll, they harness light energy Similar mechanisms for synthesizing and inserting membrane proteins Proteasomes of similar constructions Differences of Two Cell Types Eukaryotic cell Prokaryotic cell Division of cells into Nucleoid nucleus and cytoplasm Complex Ribosomes Cells are able to evolve if we look at membranous cytoplasmic housekeeping genes, e.g, enzymes organelles needed from glycolysis, all those enzymes are found in all organisms both Specialized No specialized prokarytic/eukaryotic. Looking at those cytoplasmic organelles for sequencing, there are more things organelles photosynthesis common between all living organisms. mitochondria and photosynthesis Meaning we can trace it back in evolution through LUCA. LUCA is a term used in Cytoskeletal system Simple compositions Phylogenetics in which we can trace the (may move through of locomotory branch points of one organism to another. flagella/cilia) organelles - flagellin Complex flagella and Peptidoglycan cell Two Kinds of a Cell cilia wall (Rigid Cell Wall) 1. Eukaryotic Cell 2. Prokaryotic Cell Phagocytosis Asexual reproduction Similarities of the two Cellulose cell walls Plasma membrane of similar construction Sexual reproduction Genetic information encoded in DNA using identical genetic code ○ Same codon preference - codons Type of Prokaryotic Cells found in prokaryotes that may code 1. Domain Archaea different amino acids that might be a. Species that live in extremely different of those found in inhospitable environments eukaryotic b. They are often referred to as Similar mechanisms for transcription and “Extremophiles” translation of genetic information c. Methanogens - prokaryotes ○ They both have ribosomes, they capable of converting CO2 and H2 both have transcription gases into methane (CH4) gas machineries d. Archaic - lives in extreme Shared metabolic pathways conditions, such as halophiles, ○ Both do respiration, the only thermophiles, cryophiles, and often difference is energy source referred to as extremophiles, such Similar apparatus for conservation of as methanogens that can chemical energy as ATP synthesize methane gas from 3  carbon dioxide and H2 gases. on a small number of “representative Depending on the organisms models.” involved, they can be used in carbon production and absorption in the environment. 2. Domain Bacteria a. Includes the smallest known cells in the world - mycoplasma b. Lack cell walls (A) Arabidopsis thaliana - apatella for the c. A genome with fewer than 500 production of petals genes (B) Yeasts - easily reproduced due to its size d. Present in every conceivable (C) C. elegans habitat on Earth. Even in the (D) Drosophila - their eyes can be found at the respiratory tract, gastrointestinal, back, if the disks are swapped. and skin. (E) Mice and Rabbits (Mammals) - for testing we usually use Sprague rats Type of Eukaryotic Cells (F) Danio rerio (zebra fish) - can be used for In many regards, the most complex research eukaryotic cells are not found inside of plants or animals, but rather among the How smol is small? unicellular protists An alternate pathway has led to the evolution of multicellular organisms in which different activities are conducted by different types of specialized cells As a result of differentiation, different types of cells acquire a distinctive appearance and contain unique materials. ○ E.g. bones - bones are made up of calcium, and it allows the reproduction of red blood cells and the rigidity of the bones. Two units of linear measure are most commonly used to describe structures within a cell: the micrometer (μm) and nanometer (nm). One μm is equal to 10^-6 meters, and one nm is equal to 10^-9 meters. The angstrom (Å), which is equal to one-tenth of a nm, is commonly employed by molecular biologists for atomic dimensions. One angstrom is roughly equivalent to the diameter of a hydrogen atom. Model Organisms Cell and molecular biologists have Special Topics: Viruses, Stem Cells and focused considerable research activities Endosymbiosis 4 Viruses Responsible for dozens of human Viroids diseases, including AIDS, polio, An infectious agent consisting of a small influenza, cold sores, measles, and a circular RNA molecular that totally lacks a few types of cancer. protein coat. ○ HIV is the virus of AIDS. T.O. Diener coined the term viroid. Occur in a wide variety of very different The RNAs of viroids range in size from shapes, sizes, and constructions, but all of about 240 to 600 nucleotides, one tenth them share certain common properties. the size of the smaller viruses. All viruses are obligate intracellular Viroids - Obligatory Parasites; Small RNA parasites; that is, they cannot reproduce virus, smaller than Viruses. They are unless present within a host cell. already RNA, they can easily infect one Virus is a genetic material coated with cell to another since they are ready for protein, this genetic material might be translation. Viroids can slip through RNA or DNA. As they enter the host, they connecting appendages of the cell. are able to release the genetic material into the cytoplasm of the host to translate. Stem Cells These proteins may be able to replicate Hematopoietic stem cells in the bone and be coated inside the cytoplasm. They marrow are an example of an adult stem explode inside and infect other cells. cell Obligatory parasites - they need a host Stem cells are defined as to thrive undifferentiated cells that ○ Are capable of self-renewal, that is, production of more cells like themselves, and ○ Are multipotent, that is, are capable of differentiating into two or more mature cell types Inside the bone marrow, we have Hematopoietic Stem Cells or Adult Stem Cells, they do not differentiate because it Depending on the specificity of the virus, is essential to constantly replenish the the host may be a plant, animal, or amount of RBCs in our bodies. They bacterial cell. produce nucleated RBCs, once done, they Outside of a living cell, the virus exists as are out o the Hematopoietic Stem Cells a particle, or virion, which is little more Once the RBCs are found in the than a macromolecular package bloodstream, they are slowly being Sometimes, we have viruses that can endonucleated. affect multiple targets. Outside of a living cell, it can only exist as a virion. This virion can be destroyed by a lot of objects or dehydration that can be associated with sanitization. Embryonic Stem Cells 5  Embryonic stem (ES) cells, which are a Endosymbiont Theory type of stem cell isolated from very young Ancestral eukaryotes came from large mammalian embryos prokaryotes that ingested aerobic The egg would be allowed to develop to prokaryotes. an early embryonic stage, and the ES Mitochondria - The prokaryotes are able cells would be removed, cultured, and to create energy without energy that induced to differentiate into the type of becomes mitochondria. The heterotrophic cells needed by the patient prokaryote digested food that gives food Ethical considerations to the mitochondria. Chloroplast - Photosynthetic cyanobacteria entered the macrophage Induced Pluripotent Stem Cells The cells are not initially totipotent but pluripotent, plural, it can differentiate into multiple functions. Unlike ES cells, the generation of iPS cells does not require the use of an embryo. Week 2 | The Cellular Basis of This feature removes all of the ethical Life reservations that accompany work with ES Microscopes cells and also make it much easier to developed for clearer view of cells and generate these cells in the lab. cellular structure Undifferentiated iPS cells may give rise to The first microscopes were Light teratomas. Microscopes (LM), visible light passes The usage of chemicals may activate through a specimen, then through glass cancer genes is the sought problem lenses, and finally is projected into the viewer's eye Light microscopes can magnify effectively to about 1,000 times the actual size of the specimen Parameters in Microscopy 1. Magnification - is the ratio of an object’s image size to its real size (increase in an object's image view compared with its actual size. 2. Resolution - is a measure of the clarity of the image; it is the minimum distance two points can Endosymbiont Theory 6 be separated and still be distinguished as separate points. Microscopes have limitations human eye and microscope have limits of resolution–the ability to distinguish between small structures Therefore, the LM cannot provide the details of a small cell structure. Depth of field - can be increased to improve focus In 1950s, scientists started using the electron microscope (EM) to view the ultrastructure of cells Instead of light, EM uses a beam of electrons EM can: ○ resolve biological structures as small as 2 nm ○ can magnify up to 100,000 times Types of Electron Microscope 1. Scanning Electron Microscope - detailed architecture of cell surfaces 2. Transmission Electron Microscope - details of internal cell structure Differential interference (LM) amplifies differences in density so that structures in living cells appear three-dimensional. Using LM, scientists studied: microorganisms animal and plant cells some structures within cells In 1800s, studies lead to cell theory which states that all living organisms are composed of cells these cells arise from pre-existing cells Small size of cells relates to the need to exchange materials across the plasma membrane. 7 Cell size must be large enough to house DNA, proteins, and structures needed to survive and reproduce but remain small enough for an efficient Surface-Volume (SV) ratio. Parts of a Prokaryotic Cell Plasma membrane Functional Compartments of Eukaryotic Cells 1. The nucleus and ribosomes are responsible for genetic control. 2. The endoplasmic reticulum, lysosome, vacuoles, and peroxisomes are responsible for the manufacture, Parts of a Eukaryotic Cell (Animal and Plant) distribution, and breakdown of molecules. 3. Mitochondria in all cells and chloroplasts in plant cells are involved in energy processing. 4. Structural support, movement, and communication between cells are functions of the cytoskeleton, plasma membrane, and cell wall. Nucleus most noticeable organelle in a cell separated by a nuclear envelope DNA is separated into chromatin fibers with histone proteins (octamer for supercoiling of DNA) 8  studded with of nuclear pores for transfer ER, Golgi, Lysosomes function in the distribution of DNA of materials. ○ Retroviruses can surpass… ○ can be managed through CRISPR (gene-editing) and stem cell Endoplasmic Reticulum Largest component of ES Ribosomes Extensive network of flattened sacs and involved in cell protein synthesis tubules responsible in creating the polypeptide Smooth ER: no ribosomes used for translation to proteins Rough ER: w/ ribosomes cells that make a lot of proteins have a ○ Growing polypeptides grow here. large number of ribosomes (e.g., Protists Glycoprotein binds folding. undergo polycistronic transcription: mRNA codes for more than one protein ) The ER is a biosynthetic workshop In eukaryotes, they are monocistronic SER: lipids store Calcium ions because the mRNA codes for only one RER: marks additional membrane & protein. secretory proteins some are free (in the cytosol), some are bound to the endoplasmic reticulum or nuclear envelope Endomembrane System Cytoplasm - region between the plasma membrane and the nucleus ES components are suspended in the cytosol Region where cell metabolic processes occur Some are physically converted …. 1. Nuclear envelope : synthesis 2. ER, Golgi apparatus, lysosomes: distribution Golgi Apparatus 3. Vacuoles : storage Molecular warehouse & processing station 4. Plasma membrane: export of molecules for products manufactured by ER Ships in the forms of vesicles; has Many organelles are connected in the receiving and shipping side Endomembrane System (ES) Many membranes are part of the ES Some membranes are physically connected, or pinch off as vesicles The ES includes Nuclear envelope - synthesis ER Golgi apparatus - detects where material will go; sorting center Lysosome - vesicle containing enzymes that degrade food Vacuoles - storage Plasma membrane - export of molecules 9  mRNA → nuclear pore → translated by ribosomes in the RER → polypeptide chain/ protein is synthesized in the RER → Golgi Apparatus identifies the tag and sorts → secretes as a vesicle Lysosome Membrane-enclosed sac of digestive Mitochondria enzymes made by RER and processed Carry out cellular respiration in all in the Golgi Apparatus eukaryotes Fuse w food vacuoles & digested food Cristae enhances surface area which Destroy bacteria engulfed by WBCs increases ATP production Fusse w/ other vesicle containing Cellular respiration converts chemical damaged organelles for recycling energy in the form of ATP Chloroplasts Convert light energy to chemical energy of sugar molecules Photosynthesizing organelles of plants & algae Vacuoles Large storage spaces Some protists have contractile vacuoles, which eliminate water from the protists The Endomembrane System 10 Mitochondria & chloroplasts have own DNA Microtubules (Endosymbiont Theory) Shape & support *anaerobic* bacteria & *anaerobic* Tracks along which organelles quipped photosynthetic eukaryote with motor proteins move Grow out from centrosomes, which contain a pair of centrioles 25 nm in length Intermediate Filament Reinforce cell shape, anchor some organelles Often more permanent fixtures in cell Does not undergo repair once broken but instead is replaced in sets 10 nm Microfilaments Support cell shape Motility 7 nm in diameter The Cell’s Internal Skeleton Cilia & Flagella Cytoskeleton - network of protein fibers, Cilia - propel protists organizes structures ○ Other protists may move using Microtubules - made of tubulin flagella; longer than cilia and Intermediate filaments - fibrous protein limited to 1 or a few Microfilaments - actin filaments Both are composed of microtubules wrapped in an extension of the plasma membrane 9+2 pattern: a ring of microtubule doublets surround a pair of central microtubules 11  Scaffolding For Biochemical Activities There are some proteins embedded on the membrane that act as chaperones for proper folding of the mechanisms and amino acids. o E.g., Pieces of amino acid and polypeptide chain sent by Golgi apparatus can form one functional protein in a form of subunit ▪ Subunits – forms proteins that are functional and could send certain signal or have Dyneins move by bending motor proteins enzymatic functions called dynein feet Proteins found on the cell surface acts as a scaffolding for the recruitment of other ○ These feet attach to and exert a proteins. sliding force on an adjacent o These other proteins can recruit more doublet proteins in a process called molecular ○ This “walking” causes the docking. ▪ Molecular docking – microtubules to bend technique used to look into ○ Releases ATP when used protein assemblies and how they occur real time; how to trigger certain assemblies to Summary make certain reaction Genetic control: nucleus, ribosome function/happen more inside Manufacture & storage: ER, Golgi, the cell Lysosomes, Peroxisomes E.g., Assemblies for Signal Energy Processing: mitochondria, transduction/Nerve chloroplast Impulse – available for scaffolding Structural Support: cytoskeleton Movement: cilia & flagella Selective Permeability Protein found in cell membranes only acts in places where only certain materials can enter and exit the cell – specifically those materials Week 3 | The Cell Surface needed in catabolism or anabolism. o E.g., Carbohydrates, for Enzymatic The Cell Surface Activities (like antibodies) An Overview of Membrane Functions Solute Transport in Osmosis Studies on Plasma Membrane Structure Go towards hypertonic environment – to The Chemical Composition of Membranes higher solute concentration When cell enters: An Overview of Membrane Functions o In Hypotonic Solution – water goes inside the cell Compartmentalization o In Isotonic Solution – level is equal; no One of the main functions of membrane pressure The cell is in itself is a system, a o In Hypertonic Solution – solute is microenvironment for the organelles, abundant in the environment, water separated from the rest of the human body. goes out to the environment o What happens inside one cell does not affect the cell adjacent to it, unless Responses to External Stimuli signaling is present. Virions and Viroid in Plants ▪ E.g., Tubers – presence of o Do apoptosis (programmed cell death) non-photosynthetic cells in a Since plants don’t have an immune system, plant together with a once bacteria, fungi or pathogens are present, photosynthetic cell. They have those affected cells and the cells adjacent to it low photosynthetic efficiency kill themselves to not spread and only localize because of non-expressive the pathogenic effect. chlorophyll; thus it is mainly for storage for photosynthetic Intercellular Interaction products. E.g., Exchange of impulses in nerves Compartmentalization is brought about by the o Such as use of sphingolipids – properties of cellular membranes. particular in nerve function 12 Energy Transduction cell can interact with the Potato – plant that is not green although all environment cells of plants have chlorophyll E.g., exposure to heat o Due to inactivated chlorophyll – do not induces production of contain a lot of magnesium heat shock proteins o However, food is stored in these types which will protect the of plants where starch and other cell from heat carbohydrates are produced by photosynthesis (occurring in The Present Fluid Mosaic Models photosynthetic materials like leaves) o Cell in these plants are able to pass down all of the produced starches to the tubers. ▪ Thus, they can transform chemical energy from leaves to tubers to form tubers. Studies on Plasma Membrane Functions Ernst Overton Pioneer of the theory of the cell membrane Made experiments using plant roots to test Peripheral protein – found in one side of the layer permeability. Integral protein – transcending both layers of the cell More lipid-soluble, easy entrance to the cell Glycolipids/Glycoproteins/Oligosaccharide – these are responsible for transferring information and acts as Evert Gorter and Francois Grendel signaling; they are detected by the receptor of the Used red blood cells to measure the amount adjacent cell of surface area a lipid would cover. o Speculated that the actual ratio was 2:1 (ratio of lipid to surface area of the Chemical Composition of Membranes cell) ▪ Langmuir trough – a lab Chemical Composition of Membranes apparatus where they Membranes are lipid-protein assemblies discovered that in the moving Held together in a thin sheet by noncovalent pan, 2/3 of the pan becomes bonds in a bilayer fashion the cell's lipid, while 1/3 is the o Presence of two layers formed by actual cell amount. hydrophilic head (faces inward in cell Thus, it was deduced that the plasma environment and outward in outside of membrane contained a bimolecular layer. cell) and hydrophobic tail (found Hugh Davidson and James Danielli inside of lipid bilayer) Lipid bilayer that was lined by a layer of They contain a wide diversity of lipids, all of globular proteins which are amphipathic. o Provide selective permeability to the Three main types of membrane lipids: cell phosphoglycerides, sphingolipids, and ▪ Protein pores – some are cholesterol. embedded in both layers, some are found in an integral Phosphoglycerides position (one side), some are Contain a phosphate group esterified to found embedded in lipid glycerol bilayer’s tail. o Esterified – covalent bond with C=OO Structure: Jonathan Singer and Garth Nicolson o Fatty acid chain esterified – Fluid mosaic model hydrophobic tail – 16-22 carbons o Mosaic – Due to globular proteins o Varying hydrophilic head – dictates the span the membrane either embedded properties of the phosphoglycerides – on one layer or two PC, PS, PE, PI ▪ Random distribution of proteins o Fluid – Proteins embedded in membrane changes depending on how it reacts in the environment ▪ Protein serves as an interaction/signal to which the 13  Heads are sometimes sugar-coated or alcohol Only two of the hydroxyl groups of the glycerol o Sphingosine – amino alcohol along are esterified to fatty acids; the third is with hydrocarbon chain esterified to a hydrophilic phosphate group. o Ceramide Possess an additional group linked to the o Sphingomyelin – long chain with phosphate. phosphate group Each of the additional group forms a highly The less abundant class of membrane lipids water-soluble domain at one end of the Derivatives of sphingosine, an amino alcohol molecule, called the head group. that contains a long hydrocarbon chain o The properties depends on the head (Ceramide). group. Various sphingosine-based lipids have At physiologic pH: additional groups esterified to the terminal o PS and PI have an overall negative alcohol of the sphingosine moiety: charge – can interact covalently with 1. Sphingomyelin – positively charged amino acids found phosphatidylcholine substitution. in embedded proteins 2. Glycolipid – carbohydrate o PC and PE are neutral substitution. Member fatty acids may be saturated, - Cerebroside monounsaturated, polyunsaturated. - Ganglioside o Essential for its ability to be tightly ▪ Presence of sugars are useful packed and loop into a spherical for transmitting information shape. (impulses from one neuron to ▪ Saturated – saturated by another) hydrogen atom; 4 covalent Similar to phosphoglycerides but have longer, bonds can be attached highly saturated fatty acyl chains ▪ Monounsaturated – 1 carbon o However, high levels of sphingolipids atom can bind due to in membrane can cause cholera presence of double bonds infection and botulism – damaging ▪ Polyunsaturated – many for CNS double bonds present Glycolipids play crucial roles in nervous cell Example: function (galactocerebroside) o EPA and DHA – Both have long Glycolipids may be a route for infection by carbon fatty acids cholera and botulism o However, double bonds causes unsaturation – shortening of distance of carbon molecules ▪ HDL – unsaturated; good cholesterol Cholesterol LDL Fifty percent of the lipid molecules in the plasma membrane. o Most are globular in shape – smaller in size but interact the most with the protein groups – fill in gaps to hold together protein members found in plasma membrane Small hydrophilic hydroxyl group toward the Sphingolipids membrane surface. 14  The hydrophobic rings of a cholesterol Integral proteins- Sometimes contain molecule are flat and rigid, and they interfere sugar molecules to become glycoproteins. with the movements of the fatty acid tails of the phospholipids. The sugar molecules are responsible for signaling, they can be perceived by a These three lipid membranes depend on the receptor and the receptor will react with temperature and environment and change in the sugar molecule. The receptor is a type proportion as they react based on the environment in which the cell is placed. of protein, in the protein, or the amino acids will interact with the amino acid residue found within the integral protein Phospholipid Bilayer Membrane and as it interacts the protein will change its conformation forming a fold of integral protein, There will be changes if naagkarron ng fold sa intracellular space, magkakaroon ng active sites and doon magkakaroon ng interaction dun sa component found in cytoplasm. Surface proteins- found only in hydrophilic head and mostly hydrophilic amino acids. Useful for quick responses to stimuli Globular protein- highly compact, most of the hydrophobic materials are found inside the globular protein and the hydrophilic Protein component- different types of protein that head is found outside. Serves as a are dependent on their function, type, shape, and receptor and also changes the where it is located within the lipid bilayer components of the bilipid layer (kung Protein channel- barrel domain (a dadagdagan ba ang cholesterol or combination of beta and alpha helixes sphingolipids). All the components are found within the center of cells) contains a gradually and constantly changing, it is lot of amino acid residues that are dynamic because of the globular proteins hydrophobic. However, on both ends of a-helix proteins (integral)- unlike the barrel-like structure, they have peripheral proteins they maintain their hydrophilic amino acids (they are found in tertiary structure. They are secondary or extracellular space and intracellular space tertiary structures and also can recruit and can interact with the hydrophilic other components later on that are found heads of lipids). The hydrophobic barrel is in the vicinity of the cell. found interacting with the hydrophobic tails of the lipid bilayer. The protein Interactions of Cells with their channel is responsible for the entrance Environment and exit of materials within the cell and the exchange of materials sometimes from Overview one cell to another. The extracellular matrix Peripheral proteins- only found in one Cell interactions with extracellular location of the cell. They have a materials hydrophobic tail that anchors it to the Cell-to-cell interactions bilipid layer. Interacting with only one lipid Tight junctions, Gap junctions, and layer or one side of the lipid bilayer. Plasmodesmata Responsible for molecular docking, they Cell Walls recruit other components, other proteins, or other enzymes that can cascade The extracellular matrix information within the cell. The Glycocalyx 15  - The layer of carbohydrate projections (sugar molecules that are bound in proteins, lipids, and other components of plasma membrane) that cover the outer surface of the membrane. - Functions: Mediate cell-cell and cell-substratum interactions- the sugar molecule or carbohydrate molecules depend on the carbon length or the conformation (is it levorotatory or dextrorotatory), and also the location of the hydrogen (saan nakakabit ang OH group). Different stimuli will react to different receptors, all those materials will be responsible for the signaling of cells. Mechanical protection to - The glycocalyx is found in the immediate cells- another layer of vicinity near the basal membrane found in protection to the bilipid plasma membrane layer - If may sugar located in the material, it Barrier to particles serves as a signaling component for Bind regulatory factors on certain stimuli the cell surface The Extracellular Matrix - An organized network of extracellular materials that is present beyond the immediate vicinity of the plasma membrane. Responsible for information transfer and movement of some cells and differentiation. - ECM is essential in skincare. Why is vitamin C oral more effective than collagen supplements? - Provides both physical and biochemical signals that can play key regulatory roles in determining the shape and activities of the cell. 16  2. Chains wound, and form a rod-like triple helix (non fibrous form that is useful in scaffolding) The best defined extracellular matrices is the basement membrane (or the basal lamina), a continuous sheet 50 to 200 nm thick that: - (1) surrounds nerve fibers, muscles, and fat cells The a-helices in protein found within the bilipid - (2) underlies the basal surface of layer as we extend it, can be entwined with epithelial tissues, such as the carbohydrates to form the collagen. epidermis of the skin or the lining of the digestive and respiratory tracts (responsible for the exchange of gases), and; - (3) underlies the inner endothelial lining of blood vessels- in the blood vessels, the transfer of nutrients happens, from the bloodstream to the different locations of the cell. How impulses are able to transverse between nerve fibers and muscle fibers. And also how Fibril Collagen fat is signaled to be stored in your Types 1-3 are able to form fibril-like adipose tissues. material that serves as a scaffolding/net Functions include: for other extracellular matrix. - Mechanical support for the Strengthened by protein crosslinks of attached cells, lysine and hydroxylysine. - Generate signals that maintain cell Type 3 - essential for maintaining other survival, components of the ECM (scaffolding). - Serve as a substratum for cell Destroyed/Damaged Collagen = no ECM migration, or low ECM. - Separate adjacent tissues within an organ, and; Non Fibrillar Collagen - Act as a barrier to the passage of Type 4 - membrane that provides macromolecules. mechanical support that are able to trap fibrial collage. Molecules of the ECM - Collagen Found in basement membranes and are Ubiquitous; fibrous glycoproteins only serves as a lattice for deposition of EC found in ECM. materials. Although there are various types, there are two important structural features: [Question: “Why is it not effective or useful when 1. 3 Trimers called a-chains (basically we eat collagen?” glycoproteins) 17 Answer: Due to collagen being a glycoprotein, it Contains Hyaluronic acid - responsible for will only be digested by the body. It is better to imbibing a lot of cations including water consume vitamin C rich foods because it is essential in forming or production of collagen. It is Arbitrary/Core protein mainly essential in crosslinking lysine and location where you can see protrusions of hydroxylysine.] Carbohydrates Carbohydrates = contains Molecules of the ECM - Proteoglycan glycosaminoglycans that are covalently bonded Contains Keratan sulfate and Chondroitin sulfate - since sulfate sila, acidic sila Ex. Pitted scar (sira yung ecm) Once you apply Hyaluronic acid, you restore your ECM by tending a layer beneath the damaged skin. Once applied, the damaged skin will be replaced by the new flatter skin. The ECM of bone has proteoglycans impregnated with calcium phosphate salts hence the hardened structure. Molecules of the ECM - Fibronectin Proteoglycan - a polysaccharide complex. Proteo = Protein, Glycan = Polysaccharide Able to produce complexes that imbibe water. Composed of 2 polypeptide chains that are paired Able to produce porous material for at their c-terminal bisulfur containing amino acid hydration, in order to be able to resist residues. compression and also be able to form a Contains a lot of domains that are able to protective layer in the cells. change their conformation depending on Serves as the suppleness of the skin. what other ECM materials are able to bind Proteoglycans form a porous, hydrated gel to it. that fills the extracellular space like Near the NH2/Amino/N terminal packing material which resists 1. Heparin- and fibrin-binding compression forces. domain Sulfated GAGs bind huge numbers of 2. Collagen-binding domain - cations, which in turn bind large numbers essential for anchorage of of water molecules. fibronectin to the ECM 3. Cell-binding domain Basal protein 4. Heparin-binding domain location where the Arbitrary protein binds. Composition of fibronectin: 18  1. Highly variable based on follow different routes from one part of the the specific amino acid they embryo to another. contain. 2. Specific amino acid - responsible to bind only to specific types of collagen, cell, or fibrin. Receptive to certain ECM materials. Molecules of the ECM - Laminin Each of the two polypeptide chains should be able to contain: 1. Binding site for numerous components of the ECM, such as collagens, proteoglycans, and other fibronectin molecules. 2. Binding site for receptors on the cell surface. These binding sites hold the ECM in a stable attachment to the cell. Responsible for neural development and differentiation Extracellular glycoprotein Compromised by a primer Cell signaling; able to sort cells - certain receptors are observed by the cells (receptors help locate where cell differentiation can occur). – end of slide 15– Integrin Activation Fibronectins serve as a signal for the Integrins can be activated rapidly by movement of the cell. different ECM materials as they interact The importance of fibronectin and other with the extracellular head. extracellular proteins is particularly evident during embryonic development. During the development of a fetus, we have what we call ‘Initial development’ which brings about maternal effect genes. These maternal effect genes are then being transcribed and translated, in order for it to be interacted with fibronectins. The fibronectins will then be able to move in certain parts of the cell forming ‘Spatial differentiation’. Development is characterized by waves of cell migration during which different cells 19  ○ The integrin is attached to ECM peptides. If the RGD peptides are present, like collagen and fibronectin. it caps the integrins and it signals cells not ○ The conformation of the head to aggregate (e.g. platelet aggregation) changes. ○ The conformed head will change Focal Adhesions and Hemidesmosomes the conformation of the Focal adhesions occur at a minimal rate, cytoplasmic tail. that is found in vitro ○ The cytoplasmic tail will recruit Once the cell makes contact with the materials such as vinculin, actin substratum, the cell flattens and spreads and talin itself out there, which resembles neurons ○ These materials will be able to and is responsible for neural development recruit enzymes such as Focal Focal adhesions contain large clusters of Adhesion Kinase (FAK) and integrins which are connected by various Steroid Receptor Coactivator (Src) adaptor proteins to actin filaments ○ FAK as an enzyme will be able to ○ The surface of these integrins can convert maturase, and will cascade perceive their attachment to ECM signals until it reaches a certain E.g. responsible for the material that can be perceived by implantation of embryos in the nucleus for transcription of the placenta certain material in response to Focal adhesions may act as a type of specific stimuli sensory structure; and play a role in cell locomotion Signaling Pathways: When a cell adheres to the placenta, it Inside-out signaling: signal starts inside can absorb extracellular materials from the the cell placenta and interact with actin filaments ○ Talin binds to the integrin's in the cytoskeleton. This allows the cell to cytoplasmic domain, inducing a change shape and conform to its conformational change that environment, hence didikit siya sa activates integrins to interact with placental womb. extracellular ligands. Outside-in signaling: signal starts During the process of focal adhesion outside the cell from the ECM or external formation: ligands such as collagen or fibronectin ○ Talin undergoes a conformational ○ The extracellular domain of an change that exposes binding sites integrin binds to an external ligand, on talin's rod domain there is a conformational change at ○ Vinculin binds to these exposed the opposite, cytoplasmic end of sites which promotes the assembly the integrin, especially the beta of additional actin filaments subunit which initiates a cascade of events leading to the Hemidesmosomes are adhesive polymerization of actin filaments of structures found in vivo, anchoring cells to the cytoskeleton the underlying basement membrane. Are thicker and consist of stronger Many ECM proteins bind to integrins proteins such as keratin which is because they contain the amino acid pre-produced and doesn’t rely on external sequence arginine-glycine-aspartic acid factors for maintenance of its structure. (RGD) A common analogy is hair care: when you RGD is present in the cell-binding sites of use treatments like shampoo, conditioner, proteoglycans, fibronectin, laminin, and or even rebonding, you are interacting various other extracellular proteins with the ECM of the scalp and hair Integrins are also responsible for the follicles. These treatments can influence information found within the RGD keratin production, altering the shape and 20  structure of hair (e.g., making hair Able to select signal based on the straighter or curly by modifying the ECM glycoproteins found in the adjacent cell and introducing specific proteins like o Ex. the signal says that we are fibronectin and sulfur-containing amino of the same type of cell acids). (epithelial), deciding the kind The binding of integrins to extracellular of reactions needed (whether ligands can activate protein kinases, to adhere or not) initiating a chain reaction that transmits ▪ Selectins in red blood cells detect specific signals throughout the cell. residue: arginine, glycine, aspartic acid Week 5 | Cell to Cell Interactions residue and triggers conformation change Selectins in the cytoplasmic Selectins comprise a family of integral membrane domain, recruiting glycoproteins that recognize and bind to a particular materials for arrangement of sugars in the oligosaccharides that adhesion. project from the surfaces of other cells. Selectin types Selectin contain different types depending on size of their structural domain 1. E-selectin - endothelial cells o Moderate length 2. P-selectin - platelets; endothelial cells. o Longer length o responsible for the adhesion/ non- adhesion of the cell 3. L-selectin – leukocytes o Shorter length to squeeze in the vessel walls and determine if they are to phagocytize pathogens found in 4 Types of Domains inflammation or within clotting. o Selectins mediate transient 1. Small cytoplasmic domain interactions between circulating found in the tail of proteins within the leukocytes and vessel walls at sites cytoplasmic side of the bilipid layer of inflammation and clotting. 2. Single membrane- spanning domain Bonding to ligand is facilitated by calcium responsible for the anchorage within (e.g., glycocalyx, information on the ECM) the cell’s domain/ membrane o If it does not identify glycoprotein, it becomes connected via calcium ions o The bond formed becomes stronger 3. Large structural domain when placed under mechanical stress Contains different sizes that is ▪ Ex. Wounds under responsible to reach the selectin mechanical stress (cut or large extracellular segment consists of bleed), RGN protection of the a number of separate modules, platelets will be lost, hence it including an outermost domain that sticks together to act as acts as the lectin sealant to prevent the 4. Lectin-like domain bleeding Detect certain oligosaccharides or Immunoglobulin glycoprotein Contain active sites that are able to interact and distinguish certain glycoprotein o Ex. carbon found in glycoprotein, conformation, linearity 21