Cell Membranes

BIO 224 Introduction to Molecular and Cell

Biology

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

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

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

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

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

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

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

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

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

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

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

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

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

Bilayer structure of the plasma membrane

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

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

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

Lipid components of the plasma membrane

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

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

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

Fluid mosaic model of the plasma membrane

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

Solubilization of integral membrane proteins by detergents

Freeze-fracture electron micrograph of human red blood cell membranes

Integral membrane proteins of red blood cells

Integral Proteins

• Some transmembrane transport proteins are porins that form aqueous channels through membranes

• Some integral proteins anchored to the membrane provide for cell recognition

• Some integral proteins anchored to the membrane participate in cell signaling

Bacterial outer membranes

Examples of proteins anchored in the plasma membrane by lipids and glycolipids

Membrane Mobility

• Proteins and phosphlipids cannot move quickly between faces of the membrane

• Lateral movement through the membrane is allowed

• Membrane proteins associated with the cytoskeleton or other proteins are restricted from moving

• Plasma membranes of some cells are divided into functional domains

Mobility of membrane proteins

Membrane Mobility

• Functional domains of membranes restrict protein movement to the area with which they are associated

• Lipid rafts inhibit free diffusion of some membrane proteins

• Interaction of lipid rafts with the cytoskeleton stabilizes them

A polarized intestinal epithelial cell

Structure of lipid rafts

Glycocalyx

• Carbohydrate groups of glycoproteins and glycolipids that are exposed on the membrane surface make up the glycocalyx

• The glycocalyx provides protection for the cell surface

• Carbohydrate groups in the glycocalyx act as cell surface markers

The Glycocalyx

Binding of selectins to oligosaccharides

Small Molecule Transport

• Passive diffusion is the simplest method for molecules to cross the plasma membrane– Molecules dissolve in the bilayer to diffuse across

then dissolve in the aqueous solution on the other side

– No membrane proteins are needed– Molecule transport is down a concentration

gradient – Passive diffusion is a nonselective process

Molecule Transport

• Facilitated diffusion occurs along a concentration gradient or as a result of electric potential

• It requires proteins to mediate transport of the molecules across the bilayer

• Carrier proteins and channel proteins aid in facilitated diffusion across membranes

Active Transport• Active transport uses energy provided by

another reaction to drive uphill transport of molecules in energetically unfavorable directions

• Ion pumps are used to maintain ion gradients across membranes through active transport coupled to hydrolysis of ATP

• ABC transporters convey nutrients in prokaryotes and remove toxins in eukaryotes

Model for operation of the Na+-K+ pump

Ion gradients across the plasma membrane of a typical mammalian cell

Structure of an ABC transporter

Ion-Gradient Driven Active Transport

• Active transport driven by ion gradients couples molecule transport in an unfavorable direction with transport of another molecule in an energetically favorable direction

• Symport vs. Antiport

Active transport of glucose

Glucose transport by intestinal epithelial cells (Part 1)

Glucose transport by intestinal epithelial cells (Part 2)

Glucose transport by intestinal epithelial cells (Part 3)

Examples of antiport

Endocytosis

• Eukaryotes surround material for internalization in an area of plasma membrane that buds off internally in the process of endocytosis

• Phagocytosis: cell eating– Occurs in specialized cells– Produce phagosomes and phagolysosomes

• Pinocytosis: cell drinking– Receptor-mediated endocytosis is the best known

form

Phagocytosis

Examples of phagocytic cells

Receptor-Mediated Endocytosis

• Allows for selective uptake of specific macromolecules

• Molecules bind with receptors in clathrin-coated pits

• Pits bud to form clathrin-coated vesicles with the assistance of dynamin

• Vesicles fuse with early endosomes where contents are sorted to their destination

Clathrin-coated vesicle formation (Part 1)

Clathrin-coated vesicle formation (Part 2)

Formation of clathrin-coated pits (Part 1)

Formation of clathrin-coated pits (Part 2)

Receptor-Mediated Endocytosis

• Cholesterol uptake in mammals has provided understanding of receptor mediated endocytosis on the molecular level

• Fluid phase endocytosis also functions via receptors, allowing nonspecific uptake of extracellular fluids

• Endocytosis may also occur without the use of clathrin

Structure of LDL

The LDL receptor

Clathrin-Independent Endocytosis

• Cells may use caveolae for uptake of molecules, independent of clathrin

• Caveolin organizes creation of caveolae• Caveolae carry out receptor-mediated endocytosis

via transmembrane receptors, but cavoelin and caveolae lipids also function as receptors for molecule uptake

• Macropinocytosis may also be used to uptake fluids in a clathrin-independent manner

Caveolae

Sorting in early endosomes

Recycling of synaptic vesicles

Protein sorting by transcytosis

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