Cell membrane (Plasma Membrane) & Cellular Junctions

Plasma mebrane, Cytoskeleton (Actin, microtubules and intermediate filaments), Cadherins, Integrins

1. STRUCTURE OF CELL MEMBRANE & CELLULAR JUNCTIONS PRADEEP SINGH M.Sc. MEDICAL BIOCHEMISTRY HIMSR, JAMIA HAMDARD

2. CONTENTS Introduction of Plasma Membrane History Fluid Mosaic Model Chemical composition of plasma membrane Function of Plasma Membrane Cellular Junctions

3. INTRODUCTION Selectively permeable & helps in transport of substances with the help of proteins such as integral and peripheral proteins . Involved in a variety of cellular process such as Cell adhesion , I on conductivity and Cell Signaling . Provide mechanical strength to the cell. Cell Membrane or Plasma membrane separates the interior of cells from the outside environment. Composed of a lipid bilayer , including cholesterol which maintain their fluidity under various temperature.

4. HISTORY The cell theory was proposed by Theodor Schwann and Matthias Jakob Schleiden in the 1830s. All living organisms are composed of one or more cells. The cell is the most basic unit of life. All cells arise only from pre-existing cells. The lipid bilayer hypothesis was proposed in 1925 by Gorter and Grendel . The most accepted biological model of cell membrane was given by SJ Singer and G. L. Nicolson in 1972. First cell was discovered by Robert Hooke in 1665 using a microscope.

5. FLUID MOSAIC MODEL In 1972 SJ Singer and GL Nicolson proposed fluid mosaic model . Fluid – Individual phospholipids and some proteins can move sideways (laterally) in each layer-therefore FLUID Mosaic – Range of different proteins resting on the surface on through the phospholipid layer gives it a mosaic appearance.

6. CHEMICAL COMPOSITION OF PLASMA MEMBRANE

7. Cell membranes contain a variety of biological molecules, mainly lipids and proteins . Carbohydrates are present in very small amount, predominately as Glycoproteins . Composition is not set , but constantly changing for fluidity and changes in the environment. CHEMICAL COMPOSITION OF PLASMA MEMBRANE

8. The cell membranes consists of three class of amphipathic lipids: phospholipids , glycolipids and sterols . Carbohydrates are present in very small amount, predominately as Glycoproteins . Composition is not set , but constantly changing for fluidity and changes in the environment. 1. LIPIDS

9. Phospholipids are the most abundant lipids in the cell membranes. Phospholipids consists of two classes based on the types of alcohol moiety: Glycerophospholipids , Sphingolipids Plasma membrane is asymmetric I nature i.e., contains different types of phospholipids in the outer and inner leaflet ( result in increase in fluidity ) Outer leaflet: Phosphatidylcholine and Phosphatidylethanolamine Inner leaflet: Phosphatidylserine, Phosphatidylinositol & Sphingomylein Phospholipids

10. Phospholipids are amphipathic molecules consist of a polar head and unsaturated fatty acid tails. The unsaturation in the fatty acid chains prevents the close packing of the plasma membrane.

11. Glycolipids only accounts for 2% of the total lipids. The fatty acids in the glycolipids usually contain even number of carbon atoms, typically between 16 and 20. Glycolipids Cholesterol Cholesterol is normally found dispersed between the hydrophobic tails of the membrane phospholipids. Cholesterol regulates the fluidity of the plasma membrane. At high temperatures , cholesterol inhibits the movement of phospholipid fatty acid and reduced membrane fluidity . At cold temperatures , cholesterol interferes with fatty acid chain interactions. Acting as antifreeze, cholesterol maintains the fluidity of the membrane.

12. Fluidity O f Lipid B ilayer Low temperature High temperature Phase transition Fluid like organization. Polar head loosely packed Tails disordered. Membrane thinner. Gel like organization. Polar head tightly packed. Tails regular Membrane thicker

13. Plasma membranes also contain carbohydrates, predominantly  glycoproteins . Carbohydrates are located on the surface of the cell where they recognize host cells and share information. Viruses and other parasites bind to these receptors cause an infection. 2. Carbohydrates

14. Plasma membrane has large content of proteins, typically around 50% of membrane volume. 3. Proteins Type Description Examples Integral proteins or transmembrane proteins Span the membrane and have a hydrophilic   cytosolic   domain , which interacts with internal molecules, a hydrophobic membrane-spanning domain that anchors it within the cell membrane, and a hydrophilic extracellular domain that interacts with external molecules. The hydrophobic domain consists of one, multiple, or a combination of  α- helices  and  β sheet protein   motifs . Ion channels,  proton pumps ,   G protein-coupled receptor Lipid anchored proteins Covalently bound to single or multiple lipid molecules; hydrophobically insert into the cell membrane and anchor the protein. The protein itself is not in contact with the membrane. G proteins Peripheral proteins Attached to integral membrane proteins, or associated with peripheral regions of the lipid bilayer. These proteins tend to have only temporary interactions with biological membranes, and once reacted, the molecule dissociates to carry on its work in the cytoplasm. Some enzymes ,  some hormones

15. Integral protein Peripheral protein Integral proteins are permanently attached to the membrane. Embedded in the whole membrane. Serve as carrier proteins, channels, &enzymes. Detergents should be used to remove integral proteins. Glycophorin are the example of integral proteins. Peripheral proteins are temporarily attached to the membrane. Located on the inner or outer surface of the phospholipid bilayer. Serve as receptors and surface antigens. Peripheral proteins removed by salt, pH changes Erythrocyte spectrin are the example of peripheral proteins.

16. Ion channels allow inorganic ions such as sodium, potassium, calcium, or chlorine to diffuse down their electrochemical gradient across the lipid bilayer.   Ion channels plays an important role in controlling the electrical behavior of cells (i.e. nerve cells ). A G-protein coupled receptor is a single polypeptide chain that crosses the lipid bilayer seven times responding to signal molecules (i.e. hormones and neurotransmitters). G-protein coupled receptors are used in processes such as cell to cell signaling, the regulation of the production of cAMP , and the regulation of ion channels .

17. Asymmetry Of Lipid Bilayer Outer leaflets Lots of carbohydrates. Sphingomyelin and phosphotidylcholine. Floppase is an outward-directed ATP-dependent transporter. Inner leaflets Carbohydrates does not have significant role. Phosphotidylserine and phosphotidylethanolamine . Flippase is an inward-directed ATP-dependent lipid class of transporters.

18. FUNCTIONS OF PLASMA MEMBRANE Protective :- Forms outermost boundary of the cells. Digestive :-Takes in food and excretes waste products. Selective Permeability :-Helps in transport across the membrane. Contains cell surface receptors ( e.g : Glycoprotein receptors present on RBCs). Cell Adhesion Molecules ( Cadherins ) present on the plasma membrane of certain cells plays an important role in the process of inflammation. Junctions: Helps in formation of various types of junction ( Adherens & Anchoring) along with the help of cytoskeleton elements.

19. CELLULAR JUNCTIONS

20. Intercellular Connections Contents Types of Cytoskeleton Classification of junctions Tight junctions Anchoring junctions Adherens junctions Desmosomes Gap junctions

21. CELL JUNCTIONS The cell junction is a cell-cell or cell-extracellular matrix contact within a tissue of a multicellular organism, especially abundant in epithelia. Combined with cell adhesion molecules and extracellular matrix , cell junctions help hold animal cells together.

22. Eukaryotic cells contain protein filaments that are collectively called as cytoskeleton . These cytoskeleton filaments plays an important role in the establishment of Cellular Junctions . These cytoskeleton elements also helps in establishing cell shape, provide mechanical shape, help in locomotion of cell, chromosome separation, intracellular transport of organelles

23. C ellular Junctions There are t wo main ways in which animal cells are bound together . Cell – Cell Junction Cell – Matrix Junction

24. ANCHORING JUNCTIONS All four types of Anchoring junctions depends on cell adhesion molecules (CAMs). These proteins span the plasma membrane with one end linking to the cytoskeleton {cell-cell or cell – matrix}and other is exposed outside the membrane. The primary function of Anchoring junction is to resist the external forces that pull the cells apart. Cytoskeleton linked transmembrane protiens falls into four superfamilies. Cadherins <cell-cell> Integrins Immunoglobulins selectins

25. Types of Anchoring Junctions

26. Arrangement of Junctions in a Single C olumnar Epithelium Cell

27. 1. Adherens Junction Cadherins  (named for "calcium-dependent adhesion") are a type of (CAM) that is important in the formation of adherens junctions to bind cells with each other.  Cadherins  are a class of type-1 transmembrane proteins. Cadherins depends on calcium (Ca 2+ ) ions for their function.

28. Classification of cadherins Classical cadherins E-cadherin {Epithelial cells} N- cadherin {Nerve cells and the lens cells} P- cadherin {placental and epidermal cells} Non-classical cadherins Protocadherins {found in brain} Desmocollins and Desmogleins { Desmosomes}

29. Assembly of Adherens junction

30. Cadherins Mediates Homophilic Adhesion Cadherin structure and function

31. Cadherins Link Adaptor Protiens To The Actin Cytoskeleton

32. Adherens J unctions {cadherin based anchoring junction } The best understood and most common type of cell to cell anchoring junction, which employs cadherins to link the cytoskeleton to link the cytoskeleton of one cell with that of its neighbour.

33. Adherens junctions b/w epithelial cells in small intestine

34. 2. DESMOSOMES Desmos means ‘bound’ , Soma means ‘body’. It is also called Macula Adherens . Provide strong mechanical strength between the epithelial and muscle cells. These junctions are small disk shaped ‘spot welds’ between adjacent cells.

35. DESMOSOMES

36. Desmosomes , Hemidesmosomes and Intermediate filament network

37. TIGHT JUNCTION Occupies the most apical position Closely associated areas of two cells. Form a seal b/w cells and a fence between plasma membrane domains. Selectively limits the diffusion of water , ions, and larger solutes as well as migration of cells. DIAGRAMATIC REPRESENTATION OF TIGHT JUNCTION