Biochemistry - Biological Membranes

Chapter 8

Cell (plasma membrane)

- semipermeable phospholipid bilayer; chooses which particles can enter/leave cell at any point in time
- composed of 2 layers of phospholipids

Fluid mosaic model

theory that underlies structure and function of cell membrane & accounts for presence of 3 types of membrane proteins

glycoprotein coat

created by carbs associated with membrane-bound proteins (cell wall has higher levels of carbs)

Cell membranes

- protect interior of cell from external environment
- selectively regulate traddic into/out of cell
- involved in intracellular/intercellullar communication& transport
- contain proteins embedded w/in lipid bilayer
(act as cellular receptors during signal transduction & play important role in regulating/maintaining overall cellular activity)

Phospholipids

move rapidly in plane of membrane through simple diffusion

Lipid rafts

- collections of similar lipids with/without associated proteins; serve as attachment points for other biomolecules & as roles in signaling

Lipids rafts & proteins

travel within plane of membrane, but slowly

Lipids moving between membrane layers

energetically unfavorable ebcause polar head group of phospholipid must be forced through nonpolar tail region in interior of membrane

Flippases

specialized enzymes that assist in transition or ‘flip‘ between layers

Dynamic changes in concentraion of membrane protein

mediated by gene regulation, endocytotic activity, & protein insertion
[cells up/down-regulate number of specific cellular receptors on surface in order to meet cellular requirements]

Fatty acids

carbozylic acids containing hydrocarbon chain & terminal carboxyl group
[chains can be saturated or unsaturated]

Triaglycerols (triglycerides)

storage lipids involved in human metabolic processes
- contain 3 fatty acid chains esterified to glycerol molecule

Unsaturated fatty acids

- ‘healthier‘ fats because they have one or more double bonds & exist in liquid form at room temp
- in plasma membrane; these characteristics impart fluidity to membrane
- humans can only synthesize few unsaturated fatty acids, rest come from intestine inside chylomicrons
- a-linolenic acid & linoleic acid (essential fatty acids)

Saturated fatty acids

- main components of animal fats, tend to exist as solids at room temp
- ‘less healthy’; found in processed foods
- when incorporated in phospholipids membranes, decreases overall membrane fluidity

Glycerophospholipid (phospholipid)

- formed by substituting one of the fatty acid chains of triaclglycerol with phosphate group so that polar head group joins nonpolar tails
- hydrophobic interactions = spontaneous assembly into micelles or liposomes
- used for membrane synthesis
- produce hydrophilic surface layer on lipoproteins = very low density lipoprotein (VLDL) lipid transporter
- primary component of cell membranes
- serve structural roles & second messengers in signal transduction
- phosphate group provides attachment point for water-soluble groups = choline (phosphatidylcholine - lecithin) or insitol (phophatidylinositol)

Micelles

small monolayer vesicles

Liposomes

bilayered vesicles

Triacylglycerol & Glycerophospholipid structures

Sphingolipids

- important consituents of cell membranes
- don’t contain glycerol, but sturcture similar to glycerophospholipids (contain hydrophilic region & two fatty acid-derived hydrophobic tails)
- various classes differ in identity of hydrophilic regions: ceramide, sphingomyelin, cerebroside, ganglioside

Cholesterol

- negative health effects
- regulates membrane fluidity
- necessary in synthesis of all steroids (derived from cholesterol)

- large ratio of cholesterol to phospholipid = membrane remains fluid [50-50]

Cholesterol structure

- similar to phospholipids; contain hydrophilic & hydrophobic region
- occupies space between adjacent phospholipids to stabilize = prevents formation of crystal structures in membrane
- lower temp: increased fluidity
- higher temp: limits movement of phospholipids within bilayer = decreases fluidity & helps hold membrane intact
- by mass, composes ~20% of cell membrane
- by mole fraction, composes ~50% of cell membrane

Waxes

- class of lipids
- extremely hydrophobic
- rarely found in cell membranes of animals, sometimes found in cell membranes of plants

Wax structure

- composed of long-chain fatty acid & long-chain alcohol
= contibute to high melting point of these substances
- in cell membrane: provide stability & rigidity in nonpolar tail region
- serve as an extracellular function in protection/waterproofing

Proteins within cell membrane

Transmembrane proteins (transporters), embedded proteins (cell adhesion molecules), membrane-associated proteins (enzymes)

Transmembrane proteins

pass completely through bilayer

Embedded proteins

associated either with interior (cytoplasmic) or exterior (extracellular) surface of cell membrane

Integral proteins

- both transmembrane & embedded proteins
- associated with interior of plasma membrane; assisted by one or more membrane-associated domains that are partially hydrophobic

Membrane-associated (peripheral) proteins

bound to elextrostatic interactionswith lipid bilayer, at lipid rafts or other transmembrane or embedded proteins, like G proteinsfound in g protein-coupled receptors
transporters, channels, receptors are generally transmembrane proteins

Carbohydrates

- attached to protein molecules on extracellular surface of cells
- hydrophilic; interactions between glycoproteins & water form coat around cell
- act as signaling & recognition molecules

Membrane receptors

- activate/deactivate some transporters for facilitated diffusion & active transport
- tend to be transmembrane proteins; ligand-gated ion channels open a channel in response to binding of spcific ligand
- others participate in biosignaling; G-protein-coupled receptors involved in serveral different signal transduction cascades
- generally proteins, some are carb/lipid receptors (especially in viruses)

Cell-cell Junctions

- cells within tissues form cohesive layer via intercellular junctions
- junctions provide direct pathways of communication between neighboring cells or between cells & extracellular matrix
- comprised of cell-adhesion molecules (CAM)

CAM proteins

allow cells to recognize each other & contribute to propercell differentiation & development

Gap junctions (connexons)

- allow direct cell-cell communication
- often found in small bunches together
- formed by alignment & interaction of pores composed of 6 connexin molecules
- permit movement of water & some solutes directly between cells ~ don’t permit protein transfer

Tight junctions

- prevent solutes from leaking into space between cells via paracellular route
- found in epithelial cells
- function as physical link between cells as they carry single layer of tissue
- limit permeability; create transepithelial voltage difference based on differing concentrations of ions on either side of epithelium
- must form continuous band around cell to be effective (if not, fluid leaks through spaces between junctions)

Desmosomes

- bind adjacent by anchoring to their cytoskeletons
- formed by interactions between transmembrane proteins associated with intermediate filaments inside adjacent cells
- primarily found at interface between two layers of epithelial tissue

Hemidesmosomes

similar function to desmosome:
hemidesmosomes’ main function is to attach epithelial cells to underlying structures (especially basement membrane)

Passive transport

spontaneous processes that don’t require energy (negative delta-G)
- don’t require intracellular energy stores, but utilize concentration gradient to supply energy for particles to move

Active transport

- nonspontaneous processes that require energy (positive delta-g)
- results in net movement of solute against concentration gradient
- energy source can vary

Simple diffusion

- most basic of all membrane traffic processes
- substrates move down concentration gradient directly across membrane
- only particples free ly permeable to membrane
- potential energy in chemical gradient; some energy dissipated as gradient utilized during simple diffusion

Osmosis

- specific kind of simple diffusion that concerns water
- water moves from region of lower solute concentration (higher water concentration) to one of higher solute concentration (lower water concentration)
- Hypotonic, Hypertonic, Isotonic

Hypotonic solution

concentration of solutes in cell is higher than surrounding solution
[causes cell to swell as water rushes in = bursting/lysing of cell]

Hypertonic solution

solution more concentrated than cell

Isotonic

solutions inside & outside are equimolar
- doesn’t precent movement; prevents net movement of particles
- water molecules continue to move, cell will neither gain nor lose water overall

Osmotic pressure

- colligative property
- method of quantifying the driving force behind osmosis

Colligative property

physical property of solutions dependent on concentration (not chemical identity) of dissolved particles
[Examples: vapor pressure depression (Raoult’s Law), boiling point elevation, freezing point depression]

Change in water level due to osmotic pressure

Hydrostatic pressure exerted by water level in solute-containing compartment
> will eventually oppose the influx of water
> water level will rise to pont at which it exerts a sufficient pressure to counterbalance tendency of water to flow across membrane
> pressure known as osmotic pressure (II) of solution
II = iMRT

II = iMRT

II = osmotic pressure
i = van’t Hoff factor; number of particles obtained from molecule when in solution
M = molarity of solution
R = ideal gas constant
T = absolute temperature (Kelvin)

Osmotic pressure

- directly proportional to molarity of solution
- depends on presence & number of particles (not actual identity) in solution
- maintained against cell membrane (in cells)
- if pressure created by solutes in cell exceeds cell membrane capacity; lysing
- ‘sucking pressure‘ that draws water into cell in proportion to concentration of solution

Facilitated diffusion

- simple diffusion for molecules impermeable to the membrane (large/polar/charged)
[energy barrier too high for molecules to cross freely]
- requires integral membrane proteins to serve as transporters or channels for these substrates
- examples: carrier or channel protein

Carriers

open to one side of cell membrane at any given point except for occluded state (not open to either side of phospholipid biolayer)
1. substrate binds to transport protein (brief occluded state)
2. remains in transporter during conformational change
3. dissociates from substrate-binding site of transporter

Channels

- transporters for facilitated diffusion
- open or closed confomation
- open: channels exposed to both sides of cell membrane, act like tunnel for particles to diffuse through = rapid transport kinetics

Primary active transport

uses ATP (transmembrane ATPase) or another energy molecules to power transport of molecules across membrane
[maintains membrane potential of neurons in nervous system]

Secondary active transport

“coupled transport”; uses energy to transport paritcles across membrane
- no coupling to ATP hydrolysis
- harnesses enery released by one particle going down electrochemical gradient to drive different particle up gradient
- used by kidneys to, driven by sodium, to reabsorb & secrete various solutes in/out filtrate

symport

both particles flow in same direction across membrance

antiport

both particles flow in opposite directions across membrance

Membrane Transport Processes

Endocytosis

- cell membrane invaginates & engulfs material (in vesicle) to bring into cell
- initiated by substrate-binding to specific receptors embedded in plasma membrane

Pinocytosis

endocytosis of fluids & dissolved particles

Phagocytosis

ingestion of large solids (bacteria)

Vesicle-coating proteins

initiate and carry out invagination

Exocytosis

- occurs when secretory vesicles fuse with membrane; release material from inside cell to extracellular environment
- important in nervous system and intercellular signaling

Membrane potential (V_m)

- difference in electrical potential across cell membranes
[impermeability of cell membrane to ions & selectivity of ion channels = electrochemical gradient between cell exterior & interior]

Resting potential

between -40 & -80 mV
can rise to +35 mV during depolarization of cell

Leak channels

allows ions to passively diffuse through cell membrane

Sodium-potassium pump (Na+ / K+ ATPase)

regulates concentration of intracellular & extracellular sodium/potessium ions
(chloride ions participate in establishing membrane potention as well)

Nernst Equation

used to determine membrane potential from intra/extra-cellular concentrations of various ions
R: ideal gas constant
T: temperature (kelvins)
z: charge of ion
F: Faraday constant

Goldman-Hodgkin-Katz voltage equation

flows from Nernst equation; takes into account contribution of each major ion to membrane potential
P: permeability for relevent ion

Outer mitochondrial membrane

- highly permeable due to many large pores
= allow passage of ions and small proteins
- surrounds inner mitochondrial membrane, with presence of small intermembrane space between the two layers

Inner mitochondrial membrane

- restrictred permeability compared to outer mitochondrial membrane
- contains numerase infoldings (cristae)
- encloses the mitochondial matrix (where citric acid cycle produces high-energy electron carriers used in electron transport chain)
- contains high level of cardiolipin, no cholesterol

Cristae

infoldings that increase available surface area for integral proteins associated with the membrane