Structure & Functions of the Cell PDF

Cell Physiology Assoc. Prof. M.O. Welcome MD, PhD Department of Human Physiology, College of Health Sciences, Nile University of Nigeria, FCT - Abuja  Outline 1 Definition 2 Cell Components 3 Plasma Membrane 4 Intracellular Constituents  Definition The cel...

Cell Physiology Assoc. Prof. M.O. Welcome MD, PhD Department of Human Physiology, College of Health Sciences, Nile University of Nigeria, FCT - Abuja  Outline 1 Definition 2 Cell Components 3 Plasma Membrane 4 Intracellular Constituents  Definition The cell is the basic structural and functional unit of an organism, containing the fundamental constituents of life.  The cell is made up of …… Plasma Cytoplasm membrane Plasma Cytoplasm membrane It is fluidic, It contains many viscous and membrane bound contains organelles such as numerous nucleus, biomolecule centrosomes/centri s such as oles, mitochondria, proteins, ribosomes, lipids, and endoplasmic carbohydrat reticulum, Golgi es. complex, lysosomes, and The Plasma Membrane The plasma membrane is a physico-biological membrane that separates the interior of the cell from its external milieu. It is composed of phospholipids, proteins, cholesterol, and Structure of the Plasma Membrane  Components of the Plasma Membrane Membrane Lipids The entire lipid composition of the cells of an organism is called lipidome. The study of the cell’s lipidome – lipidomics. There are approximately 109 lipid molecules in the plasma membrane of a typical animal cell. There are three main groups –  Components of the Plasma Membrane Membrane Phospholipids Lipids are the most abundant lipids in all biological membranes. Each phospholipid is composed of a hydrophilic head with attached hydrophobic acyl (aliphatic) chains. Examples are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin. Structure of a phospholipid molecule Membrane Lipids Some membrane components may occur as aggregates – lipid rafts. For instance, organization of cholesterol and sphingolipids into tiny, dynamic, and ordered domains in the plasma membrane forms lipid rafts. Membrane Lipids Lipid rafts are small (10–200 nm in diameter), heterogeneous, highly dynamic, sterol- and sphingolipid-rich domains that compartmentalize cellular processes. Lipid rafts may exist as caveolae.  Membrane Lipids Caveolae are “flask-shaped” or “cup- shaped” or “inverted omega (Ω)-shaped” membrane invaginations with an open neck. Reference: Babak Razani, Scott E. Woodman and Michael P. Lisanti. Caveolae: From Cell Biology to Animal Physiology. Pharmacological Reviews 2002;54(3):431-467; DOI: https://doi.org/10.1124/pr.54.3.431 Membrane Lipidsare composed of integral Caveolae and adaptor proteins. Caveolin-1, -2 and -3 are integral membrane proteins that constitute the structural backbone of caveolae. Cavins (cavin-1, -2, -3 and 4) are support- or adaptor-proteins that regulate the formation of caveolae by modulating the functions of caveolins. Membrane Lipids A similar pit is formed in membrane and is termed “clathrin coated pit” – which is a membrane invagination, lined (i.e. coated) by clathrin protein. This invagination is one of the initial processes of endocytosis, resulting to the formation of vesicles. Functions of Membrane Lipids Cell attachment and support Cellular signaling: Lipid rafts, for instance, form scaffolds for signaling molecules and receptors that relay extracellular information to the intracellular milieu. Regulation of cellular homeostasis. Lipid rafts regulate lateral diffusion of membrane proteins in response to receptor activation, shear stress, electrical conductance, and nutrient Functions of Membrane Lipids Vesicle budding and fusion, which are important processes in exocytosis/endocytosis coupling. For example, caveolae play an integral role in receptor-mediated endocytosis. Cavins are involved in membrane remodeling. Cellular/membrane transport.  Membrane Proteins Proteome. Proteomics. The plasma membrane is composed of a plethora of different protein molecules which may either be embedded within the phospholipid matrix (integral or transmembrane proteins) or loosely associated with the cytoplasmic face of the plasma membrane (peripheral proteins).  Membrane Proteins Some proteins may be conjugated to carbohydrate residues mostly glucose, galactose, mannose, arabinose – termed glycoproteins. Examples include glycophorins. Membrane proteins maybe soluble or insoluble in fluids surrounding the membrane. On the basis of structure, proteins can be fibrous or globular. Globular proteins are widely expressed in the plasma membrane and act as enzymes, transporters and receptors. Fibrous proteins mainly provide  Membrane Proteins: Integral proteins The integral proteins are membrane- spanning proteins that have one or more portions of their structures permanently embedded in the plasma membrane. These proteins may transverse the plasma membrane once (single-pass transmembrane) or multiple times (multi- pass transmembrane protein). Integral proteins act as transporters, receptors and enzymes. These proteins provide media for ion movement across the membrane, signaling molecules, membrane  Membrane Proteins: Peripheral Peripheral membrane proteins are proteins that are associated with one leaflet proteins (cytoplasmic face) of the bilayer. Examples include G proteins, GTPases, Ras family proteins, Wnt proteins, some protein kinases etc. These proteins shuttle between the cytoplasm and inner half of the membrane, playing a crucial role in signal transduction. They anchor the plasma membrane to the cytoskeleton actin, spectrin, ankyrin, and band 4.1.  Membrane Proteins Proteins can also be classified on the basis of their functions: 1 Receptors (ion channels etc.) 2 Transporters (e.g. membrane carriers, fatty acid binding proteins, plasma lipoproteins, etc.) 3 Enzymes (phosphatases, protein kinases, ATPases, 4 esterases, and Storage proteins nucleases) (ferritin – iron-storage  Membrane Proteins Signaling: Membrane proteins can translate extra- and intra- cellular cues into meaningful signals via interaction with intracellular and extracellular molecules and receive signals from both sides of the plasma membrane. Immune defense: Membrane proteins recognize foreign bodies.  Membrane Glycome & Glycomics. Carbohydrates Carbohydrates are a class of information- encoding biological macromolecules that form integral component of the cell. The extracellular face of the plasma membrane is covered by a carbohydrate-rich layer, described as fuzzy, and often called the glycocalyx. The glycocalyx comprises glycoproteins, collagen proteins, proteoglycans and mucopolysaccharides (glycosaminoglycans). The glycocalyx is found in epithelial and endothelial cells, where the cells have to withstand a relatively high level of stress.  Membrane The oligosaccharide chain of the Carbohydrates glycoproteins gives the glycocalyx its characteristic negative charge, which is usually due to the presence of anionic oligosaccharides (e.g. heparan sulfate). This fuzzy coat serves as an attachment surface for cellular structures.  Models of Plasma Membrane Structure 2. Fluid Mosaic Model 3. Dynamic fluid- 1. Bilipid mosaic Layer model Model  Bilipid Layer Model Evert Gorter (1881–1954) and François Grendel (1897–1969) introduced this model based on certain behavioral characteristics of membrane In fluid medium, the head (polar phospholipids. hydrophilic – water loving) of the phospholipids is directed towards the fluid medium, while the tail (nonpolar hydrophobic – water repelling In biological medium, ) extends the phospholipid to thefaces head opposite direction. the exterior (exoplasmic and cytoplasmic faces or leaflets), while the tails of each of the faces (layers) are  Bilipid Layer Model The result is the formation of a continuous spherical lipid bilayer. The formation of the lipid bilayer is controlled by molecular forces – van der Waals forces, hydrogen bonds, hydrophobic, electrostatic and non- covalent interactions.  Fluid Mosaic Model Introduced by Seymour Jonathan Singer (1924–2017) and Garth L. Nicolson (1943–). Is the basic paradigm for the organization of all biological membranes. Membranes are viewed as fluids in which proteins (integral proteins) are inserted into or attached to either leaflets (peripheral proteins) of the bilipidphospholipids Some layer. may wiggle, thus the bilayer possesses a fluidic property. The to and fro movement (flip-flop – lateral & transverse diffusion) is catalyzed by lipid translocators. There are three lipid translocators. Lipid flippases are proteins that translocate lipids from the outer leaflet of the plasma membrane to the inner leaflet. Lipid floppases use energy from ATP dissociation to transport membrane lipids from the inner to the outer leaflet Scramblase facilitates the transportation (scrambling) of lipids between the two leaflets along concentration gradients. The fluidity of the lipid bilayer is due to the mobility of membrane proteins Several and types of proteins are lipids. embedded in the fluid matrix of the membrane phospholipids similar to a “mosaic”, hence the name “fluid The interspersed proteins and lipids mosaic”. undergo dynamic rearrangement via Brownian motion. Dynamic fluid-mosaic model The model accounts for the shift in emphasis from fluidity to mosaicism – indicating a nonrandom distribution of specific membrane protein and lipid clusters that form islands or microdomains via lipid-lipid, protein-protein, and protein-lipid interactions, as well as sub- and supramembrane (cytoskeletal, and extracellular matrix) interactions. Dynamic fluid-mosaic model Dynamism of the plasma membrane is the change in functions of mobility and proximity relationships of lipid, protein molecules in the plasma membrane, resulting to substantial effects on different aspects of cell communication.  Modifications of the plasma membrane Microvilli Cilia Junctional complexes The plasma membrane of some cells may be modified …  Intracellular Components The cytoplasm is a gelatinous solution comprising the cytoskeleton of the cells as well as the The organelles. cytoplasm is composed of about 75–95% water, large quantity of carbohydrate, fat, and protein molecules. Cytosol is the fluid portion of the cytoplasm. Organelles are specialized structures of the cell that have a characteristic shape and specific functions.  Intracellular Components The cytoplasm serves as a site for chemical reactions, synthesis of cellular molecules and packaging of chemicals for export. Endoplasmic reticulum (ER) The ER is a dynamic membrane-bound synthesis, transport and quality-control organelle that is an extension of the nuclear envelope and plays a variety of roles in the cell. It is made up of flattened sacs and branching tubules that are interconnected forming a continuous space inside the organelle. Endoplasmic reticulum (ER) This space is called the ER lumen (ER cisternal space). Some regions of the cytoplasmic surface of the ER are covered with ribosomes – granular or rough ER, whereas ER without ribosomes is agranular or smooth ER.  Endoplasmic reticulum (ER) However, some areas of the ER maybe partly smooth and rough, and are referred to as transitional ER. The transitional ER is a region of the ER where secretory proteins are exported to the Golgi complex. Functions of the ER  Quality control sites in the secretory cargo proteins (transitional ER).  Site of protein processing (rough ER).  Site of lipid metabolism (agranular or smooth ER). Golgi complex The Golgi apparatus is a central station of protein modification, sorting and secretion or degradation via the lysosomal pathway. It is composed of membrane-bound compartments (flattened cisternae), which are interconnected sacs in the form of a stack in the perinuclear area. Golgi complex Vesicles destined for further processing are sent from the ER to the Golgi apparatus via one side of the stack referred to as cis face – the closest portion of the Golgi complex to the ER. Proteins and lipids transiting the Golgi complex are modified by the sequential action of enzymes of the individual cisternae. Upon completion of the modification process, the Golgi complex sorts the final products of its processing. Molecular labels or tags are added by the resident enzymes of the Golgi complex to help Golgi complex The Golgi apparatus sends off the final product to various parts of the cell by budding vesicles from its trans face. Some modified proteins may be sent to lysosomes for degradation. Trafficking functions of the Golgi apparatus Peroxisomes Peroxisomes are roughly spherical and single membrane bound organelles, mediating a wide variety of biosynthetic and biodegradative reactions in the cytoplasm. Peroxisomes are synthesis machinery that produces key components of the cell. This organelle harbors enzyme required for the synthesis of ether phospholipids, bile acids, and docosahexaenoic acid (DHA). DHA is a highly polyunsaturated long chain omega-3 fatty acid that is a primary structural component of the human brain Peroxisomes Peroxisomes perform a variety of degradative reactions according to the physiological requirements of the cell and its environs. Peroxisomal enzymes found in the lumen of the organelle are important for beta oxidation of fatty acids, detoxification of reactive oxygen species (e.g. hydrogen peroxide), alcohol, polyamines, glyoxylate, and other xenobiotics. The peroxisomal resident enzyme, catalase, instantaneously processes hydrogen Lysosomes Lysosomes are acidic and dynamic organelles that mediate the degradation of extracellular and intracellular particles from endocytic, autophagic, phagocytic and secretory pathways. Cleavage reactions executed by these organelles produce amino acids, monosaccharides, free fatty acids & nucleotides. This way, it helps to recycle the components of worn out cell. Lysosomes To function effectively, the aqueous medium inside the organelle is maintained at an acidic pH ~5.0. pH in the cytosol is much higher, thus lysosomal enzyme leakage will cause disorder of cytosolic functions. Excessive leakage of lysosomal enzymes can lead to cell autodigestion. Lysosomes can degrade the entire cell through a process called autolysis. Lysosomes Mutations of the gene that codes for lysosomal enzymes cause abnormal biogenesis of lysosomal proteins – a condition generally called lysosomal storage diseases. These diseases belong to the broad category of inborn errors of metabolism, which are associated with abnormal storage of macromolecules. Mitochondria Mitochondrion is a complex oblong shaped organelle that is found in the cytoplasm of all eukaryotic cells, referred to as the power generating house of the cell. Mitochondrion possesses its own genetic machinery (DNA) and is maternally inherited. Mitochondrial DNA (mtDNA) codes for mitochondrial ribosomal and messenger RNAs, and some of the mitochondrial proteins/enzymes/complexes. Human mtDNA encodes a total of 13 proteins, which are essential for oxidative process. The remaining proteins of this organelle are Mitochondria This organelle is a power generator, converting oxygen and nutrients into energy. Mitochondrion is the major site for ATP synthesis in aerobic cells. Mitochondrion possesses an intra-organelle space (matrix and intermembrane space) containing the enzymes of the citrate cycle, enclosed by an inner membrane containing the four complexes of the electron transport chain, ATP synthase and specific carriers for metabolites. Nucleus The nucleus is a highly specialized dynamic membrane bound organelle that harbors the genetic material of the cell. The nucleus is enclosed by a nuclear membrane, which contains pores through which materials are exchanged between the cytoplasm and the nucleoplasm. The central part of the nucleus contains a dense material called the nucleolus (see Diagram on next slide). The nucleus is important for intermediary metabolism, protein synthesis, RNA Nucleus and its component parts Genetic material of the cell Nucleus The genetic materials of the nucleus - nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) – responsible for the transmission of genetic information from one generation to another, control of gene expression and protein synthesis. The nucleus contains tightly packed chromosomes with histone proteins. The chromosomes are the short nuclear rod like materials that harbor the DNA, observed when the cell is dividing. In a non-dividing cell, the DNA is found in the nuclear structure called chromatin, which is Nucleus The nucleolus is the site of ribosome synthesis. It is the nuclear domain where ribosomal RNAs and ribosomal proteins are synthesized, processed, and assembled for export. Ribosomes Ribosomes are small granular organelles that constitute the macromolecular machinery for translating the genetic code into functional proteins; they function as sites of protein synthesis. There are two types of ribosomes in mammalian cells: Cytoribosomes and Mitoribosomes Cytoribosomes are embedded in the intercellular membranes of the rough ER. Mitoribosomes are produced by the mitochondrial DNA and are located in the Subunits of the ribosome of an animal cell. The ribosome in animal cell is the 80S, which is composed of two subunits – large (60S) and small (40S) subunits. Centrosomes/ centrioles The centrosome is a dense area of the cytoplasm located near the nucleus. It is a membrane-less organelle, the core of which consists of a pair of orthogonally arranged (perpendicularly oriented) barrel-shaped cylindrical microtubule-based structures called centrioles, surrounded in a network of proteins called pericentriolar material. The centrosome is the microtubule organizing center of the cell.  Centrosomes/ centrioles Functions of centrosome include:  Helps to organize the microtubules that form the mitotic spindle in dividing cells.  It is involved in cell motility, signaling, adhesion, trafficking of biomolecules, and polarity.  The centrosome regulates cell cycle arrest and repair in response to stress. Centrioles These are a pair of self-replicating barrel-shaped cylindrical organelles located within the centrosome that serves as the center of chromosome movement during cell division. Each centriole consists of nine triplets of microtubules assembled in a spoke- like arrangement at the end of the centriole referred to as cartwheel. Centrioles are essential for the formation of cilia and flagella. Cytoskeleton The cytoskeleton is described as a dynamic interconnected network of filamentous polymers, tubules and regulatory proteins, ubiquitously located throughout the cell, extending throughout the cytosol, having both structural and functional implications on the cells and tissues of the body. Types: microfilaments (also called actin filaments), microtubules, and intermediate filaments & septin Principal components of the cytoskeleton Cytoskeleton: Intermediate filaments These are a class of fibrous proteins that play a crucial role as structural elements of the cytoskeleton that confer mechanical strength to the cell. Intermediate filaments form highly viscoelastic, non-polar, smooth, and flexible filament networks functioning as tension-bearing elements, which help to maintain cell shape. Cytoskeleton: Microfilaments These components of the cytoskeleton are solid polar rods made up of globular proteins called actin, formed by polymerization of actin monomers. Microfilament is composed of two intertwined actin strands. Cytoskeleton: Microtubules These components are dynamic polar hollow cylinders and carry out a variety of functions, ranging from transport to structural support structures that undergo continual assembly and disassembly within the cell. Their functions include maintenance of cell shape, cell movements, intracellular transport of organelles and cargoes, and the separation of chromosomes during cell division. Cytoskeleton: Septin filaments These components of the cytoskeleton are rod-like filament formed by the polymerization of the GTP-binding proteins, septins.  Cytoskeleton Functions of the cytoskeleton:  cellular transport  cell growth and division  cell differentiation  signal transduction  gene transcription  cell and organelle motility  cell shape maintenance Intracellular Vesicles Vesicles are small membrane-enclosed transport units Used to transfer molecules between different cellular compartments. Most vesicles transfer the cargo components assembled in the ER to the Golgi apparatus, then from the Golgi apparatus to various destinations. Types of vesicles include clathrin- coated, coat protein complex-I-coated, Thank You