1. Cell Membranes BIO 224 Introduction to Molecular and Cell Biology

2. Cell membranes Cell membranes separate the interior of cells from the external environment and provide for internal compartmentalization All cell types are surrounded by a plasma membrane Eukaryotic cells contain nuclei and cyto-plasmic organelles bound by membranes

3. Cell Membranes All membranes have a similar structure: phospholipid bilayer with associated proteins – Phospholipids spontaneously form bilayers in solution due to amphipathic properties The bilayer forms a stable barrier between two aqueous compartments and represents the basic structure of all biological membranes

5. Membrane Lipids 50% of the mass of most cell membranes is lipids Membranes of different structures or cell types may have varying levels and types of lipid content Bacterial membranes are less complex than those of higher organisms having fewer lipid types present Mammalian membranes contain many lipid types within their structure

7. Membrane Lipids Lipid bilayers act like two-dimensional fluids in which molecules may rotate and move laterally Fluidity is critical to membranes and is determined by temperature and lipid composition Lipids with unsaturated FAs and shorter FA chains remain fluid at lower temps Cholesterol plays a major role in maintaining membrane fluidity due to its structure – It helps support rigidity of membrane while maintaining fluidity at lower temperatures

10. Membrane Proteins Make up 25 to 75% of the mass of cell membranes Membrane structure is thought of as a fluid mosaic with proteins inserted into the lipid bilayer Phospholipids provide basic membrane structure and proteins carry out the specific functions of the membranes Proteins interact with membranes in one of three ways

11. Integral Membrane Proteins Embedded directly in the lipid bilayer Most are called transmembrane proteins – Span the entire lipid bilayer with exposed portions on both sides of the membrane – Membrane spanning portions are usually α-helical areas of 20 to 25 nonpolar AAs – Another bilayer spanning structure is the β-barrel, formed when β sheets fold into a barrel-like structure These proteins are amphipathic with hydrophilic portions exposed to the aqueous environment The proteins may span the membrane only once, or multiple times Most transmembrane proteins in eukaryote plasma membranes have added carbohydrate groups exposed on the cell surface

13. Lipid-Anchored Membrane Proteins Proteins anchored in membranes through covalent bonding with membrane lipids Particular lipid groups anchor proteins to one of the faces of the plasma membrane The hydrophobic portion of the lipid is embedded in the membrane and the protein is bound covalently to the lipid The polypeptide is not inserted into the hydrophobic portion of the membrane

14. Peripheral Membrane Proteins Attached to the membrane through interactions with integral or lipid-anchored membrane proteins, or polar head groups of the lipids Do not interact with hydrophobic interior of lipid bilayer May only bind transiently with membrane, as in signaling processes

16. Transport Across Cell Membranes Biological membranes are selectively permeable, allowing cells to control internal composition Small uncharged molecules freely diffuse across Large polar molecules and ions cannot freely diffuse across a lipid bilayer – These molecules may cross the membrane through transmembrane proteins acting as transporters Two classes of membrane transport proteins: channel proteins and carrier proteins

18. Channel Proteins Form open pores in membranes, allowing molecules of proper size and charge to cross Pores open and close in response to extracellular signals When open, pores allow molecules to freely diffuse across the membrane Ion channels allow passage of inorganic ions

20. Carrier Proteins Selectively bind and transport specific small molecules across Behave like enzymes, binding molecules and undergoing conformational changes to open channels facilitating passage of molecules across the membrane to be released on the other side

22. Transmembrane Transport Passive transport across a membrane occurs through channels or carrier proteins in an energetically favorable direction due to concentration gradients Active transport across a membrane occurs when molecules are transported in an energetically unfavorable direction in conjunction with hydrolysis of ATP as an energy source

24. Plasma Membranes All cells are surrounded by a plasma membrane The fundamental structure of the plasma membrane is the phospholipid bilayer Proteins embedded in the bilayer carry out specific functions of the membrane RBC plasma membrane studies provided the first evidence of lipid bilayer structure

25. Bilayer structure of the plasma membrane

26. Plasma Membrane Phospholipids More than half the lipid content in animal cell plasma membranes is made up primarily of four phospholipids in asymmetrical distribution – Phosphatidylcholine: glycerol phospholipid with a head group formed from choline – Phosphatidylethanolamine: glycerol phospholipid with a head group formed from ethanolamine

27. Plasma Membrane Phospholipids – Phosphatidylserine: glycerol phospholipid with a head group formed from serine – Sphingomyelin: phospholipid consisting of two hydrocarbon chains bound to a polar head group containing serine – Phosphatidylinostol is a glycerol phospholipid with a head group formed from inositol, found in minor quantities in some membranes Plays a role in cell signaling

28. Other Plasma Membrane Lipids Glycolipids are found in animal membranes with the carbohydrate portion exposed on the cell surface – Made of two hydrocarbon chains linked to polar head groups containing carbohydrates Cholesterol is a major constituent of animal cell membranes, found in equivalent amounts to phospholipids

29. Lipid components of the plasma membrane

30. Bilayer Characteristics Membrane is impermeable to water soluble molecules Bilayers composed of naturally occurring phospholipids are viscous fluids Most FA of phospholipids have double bonds that produce kinks in the hydrocarbon chains Kinks make the chains difficult to pack together and allows free movement

31. Bilayer Characteristics Cholesterol inserts into the bilayer and helps control membrane fluidity Plant cell membranes contain sterols to perform a similar function Cholesterol and sphingolipids form lipid rafts that move within the membrane – Their function is not well understood but they appear to play roles in cell movement, endocytosis, and cell signaling

32. Plasma Membrane Proteins Most plasma membranes are 50% protein and 50% lipid by weight Peripheral membrane proteins can be dissociated from the membrane by treatment with polar reagents Integral membrane proteins may only be removed by treatments that disrupt the bilayer

33. Fluid mosaic model of the plasma membrane

34. Membrane Proteins Studies of RBCs have provided information about specific proteins Most peripheral proteins in RBCs are cytoskeletal components Major integral proteins of RBCs are glycophorin and band 3 – Function of glycopohrin is not known – Band 3 is responsible for anion transport

35. Solubilization of integral membrane proteins by detergents

36. Freeze-fracture electron micrograph of human red blood cell membranes

37. Integral membrane proteins of red blood cells

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