Membrane Dynamics

Question 1

What are the functions of the cell membrane?

Answer 1

Physical barrier (separates intracellular fluid from extracellular fluid); gateway for exchange (controls movement of solutes: allows some to cross, prevents others from crossing (semipermeable)); communication (home to receptors that detect physical and chemical stimuli and starts cascade of response to stimuli); cell structure (some membrane proteins hold cytoskeleton proteins to give cell structure; may also form specialized junctions)

Question 2

Explain the structure of the cell membrane

Answer 2

Mostly made of protein (integral and peripheral) and lipid (glycolipids, phospholipids, cholesterol, sphingolipids) (ratio of protein to lipid is different for different cell types -> related to whether it is metabolically active); also contains cytoskeleton and the extracellular matrix; early model was a “butter sandwich” (layer of lipid between protein); present day it follows a “fluid mosaic” model (proteins are afloat on a sea of lipid)

Question 3

Phospholipid

Answer 3

Makes up majority of cell membrane; several different varieties (R groups, saturation); polar head groups toward aqueous sides, non polar fatty acid tails inside

Question 4

Cholesterol

Answer 4

Flat molecule, slips between fatty acid tails to fill gaps; regulates membrane fluidity (makes membrane more/less waxy; no cholesterol = loose membrane, too fluid); slows diffusion of molecules across membrane (makes it harder for other molecules to get across)

Question 5

Sphingolipids

Answer 5

Some have longer tails than phospholipids; tend to aggregate together to form lipid rafts

Question 6

Lipid rafts

Answer 6

High density of cholesterol; some proteins associate ONLY with lipid rafts, leading to areas of specialization on cell membranes (eg. some GPCRs); errors in lipid raft composition may play a role in development of some diseases such as Alzheimer’s

Question 7

What are the kinds of membrane proteins?

Answer 7

Integral (polytopic (transmembrane, more than one membrane spanning region); bitopic (transmembrane, one membrane spanning region); monotonic (permanently associated from one side)); peripheral (attached to one side of membrane by non covalent interactions; weak)

Question 8

Integral proteins

Answer 8

Permanently attached to cell membrane; polytopic/bitopic -> span the lipid bilayer once or several times; approximately 20-25 hydrophobic amino acids to span the cell membrane; monotopic -> attached from one side; may have strong hydrophobic sections that allow it to tightly associate with lipid portion of bilayer; may be modified by the addition of a fatty acid; may be electrostatic or ionic interaction between protein and phospholipid; covalently bound to an integral protein

Question 9

Peripheral proteins

Answer 9

Proteins that associate non-covalently with integral proteins, or polar heads of phospholipids; easy to purify; weak interaction

Question 10

Cytoskeleton

Answer 10

Not a membrane proteins, but often interact with them; flexible skeleton of fibrous proteins throughout the cytoplasm; at some point, interact with integral proteins (anchors and gives cell physical integrity)

Question 11

Extracellular matrix

Answer 11

Membrane proteins and secreted protein found on the extracellular side of cell membranes; forms a “husk” around cells (physically hard); highly variable glycosylation (number of different carbs added to them); contributes to physical strength of cells

Question 12

Muscular dystrophy

Answer 12

Protein dystrophin provides a link between cytoskeleton and ECM; there are many forms of MD where the dystrophin protein is affected (missing, truncated, otherwise doesn’t function correctly); results in easily damaged muscles (in severe forms, repeated damage causes muscle to eventually waste away due to incorrect interactions between proteins)

Question 13

Liposomal drug delivery

Answer 13

An emerging technology that may help issues such as drugs having low “bioavailability” due to poor solubility or some drugs being toxic at useful doses and must be targeted to a specific cell type; solid or water-soluble drugs in the core; surface proteins to target liposome to specific location in the body; surface sugars to prevent destruction by immune system; oil-soluble drugs in lipid bilayer

Question 14

Explain the evolution of liposome to lipid nanoparticle

Answer 14

It was made slightly smaller; aqueous core removed and instead tightly bound to polar heads

Question 15

Diffusion

Answer 15

Process of moving solute molecules away from an area of high concentration towards area of low concentration; passive (no external energy, just kinetic energy of molecules (usually heat)); process continues until equilibrium is reached; fast over short distances and slow over long distances (time taken to get from pt A to pt B is a “distance squared” relationship); faster at high temp; faster for small molecules; slower across a membrane

Question 16

Simple diffusion

Answer 16

No membrane; diffusion is fast

Question 17

Diffusion across a semipermeable membrane

Answer 17

Allows selected solutes to pass, but more slowly; some solutes cannot pass (rate = 0)

Question 18

What molecules can/cannot cross the cell membrane?

Answer 18

Can: hydrophobic, non-polar (O2, CO2, lipids, steroids, fat soluble molecules)
Can if small enough: small, uncharged, polar molecules (urea, H2O)
Cannot: large, uncharged, polar molecules (glucose, proteins, amino acids); charged molecules (ions)

Question 19

What determines rate of diffusion across a cell membrane?

Answer 19

Permeability across cell membrane (size -> slower when larger; lipid solubility: polar or non polar or VERY non polar); concentration gradient; surface area; temperature; composition of membrane (simple lipid bilayer vs membrane with many proteins and ECM; types of phospholipids and sphingolipids; presence of cholesterol)

Question 20

Fick’s law of diffusion

Answer 20

Rate of diffusion is proportional to surface area x concentration gradient x membrane permeability of a solute

Question 21

What is membrane permeability proportional to?

Answer 21

Lipid solubility/molecular size; changing the composition of the lipid layer can increase or decrease membrane permeability

Question 22

Intracellular fluid

Answer 22

2/3 of the total body water volume;; material moving into and out of the ICF must cross the cell membrane

Question 23

Extracellular fluid

Answer 23

Includes all fluid outside the cells; 1/3 of body fluid volume; consists of interstitial fluid (lies between the circulatory system and the cells; 75% of ECF volume) and plasma (liquid matrix of blood; 25% of ECF volume)

Question 24

Osmosis

Answer 24

Diffusion of water; water can have a concentration gradient which it will diffuse down (pure water has the “highest concentration of water”; solutes lower the concentration); movement of water can cause pressure and make cells shrink or swell

Question 25

What are the extracellular normal physiological concentrations?

Answer 25

K+: 5mM Na+: 145mM Cl-: 108mM Ca2+: 1mM Other solutes: ~31mM Total: ~290 mOsm

Question 26

What are the intracellular normal physiological concentrations?

Answer 26

K+: 150mM Na+: 15mM Cl-: 5mM Ca2+: 0.0001mM Other solutes: ~120mM Total: ~290 mOsm

Question 27

Compare these three osmolarities: (A) 1M glucose = 1 OsM (B) 2M glucose = 2 OsM (C) 2M NaCl = 2 OsM

Answer 27

B and C are isosmotic; B and C are hyperosmotic to A; A is hyposmotic to B and C

Question 28

Why is osmolarity important?

Answer 28

Cells are filled with molecules that cannot easily cross the cell membrane (such as proteins or ions), so changing osmolarity of the extracellular solution causes redistribution of water in cells (into or out of); causes cells to shrink or swell

Question 29

Tonicity

Answer 29

The ability of a solution to shrink or swell cells; (hypertonic: cells shrink; isotonic: cells don't change size; hypotonic: cells swell)

Question 30

What is the difference between osmolarity and tonicity?

Answer 30

Osmolarity describes only the number of solute molecules in a cell, and tonicity is a comparative term which describes whether a cell changes volume; osmolarity can compare any 2 solutions, and tonicity compares a solution to a cell's intracellular solution; osmolarity doesn't always tell if a cell swells or shrinks, and tonicity specifically tells if a cell swells or shrinks; osmolarity measures the concentration of ALL solutes (penetrating and non-penetrating), tonicity disregards penetrating solutes; hyposmotic solution are always hypotonic (but is not the case for iso or hyper)

Question 31

Are normal physiological intracellular solutes penetrating or non penetrating?

Answer 31

Non penetrating

Question 32

Channel proteins

Answer 32

A water filled pore; can open to both sides; eg. water channels, ion channels

Question 33

Carrier proteins

Answer 33

Never form an open channel between the two sides of the membrane; uniport carriers: one thing goes in one direction; symport carriers: two things go in one direction; antiport carriers: two things go in opposite directions; passage is open to one side, molecule binds, conformational change (transition state) closes both gates, conformational change opens the passage on the other side

Question 34

Facilitated diffusion

Answer 34

Moving a molecule across the cell membrane via a carrier protein. and the transport does not require energy other than the concentration gradient; doesn't require ATP or other solutes; this process alone cannot accumulate solute against a concentration gradient; eg. GLUT protein

Question 35

Primary active transport

Answer 35

Uses energy from hydrolysis of ATP; establishes gradients; sometimes called pumps; Na+/K+/ATPase is the most widely known eg. (but also includes Ca2+ ATPase, H+ ATPase, and H+/K+ ATPase)

Question 36

Na+/K+ ATPase

Answer 36

Pumps 2 K+ ions into cell, removes 3 Na+ ions; hydrolyses 1 ATP; several conformational changes

Question 37

Secondary active transport

Answer 37

Type of active transport; does not directly utilize ATP as a source of energy; instead, uses the concentration gradient of one molecule/ion to move another against its gradient; eg. SGLT-protein (Na+ binds to carrier; Na+ binding creates a site for glucose; glucose binding changes carrier conformation; Na+ released into cytosol, glucose follows)

Question 38

Glucose Na+ co-transporter

Answer 38

1) Na+ K+ ATPase: establishes and maintains a Na+ gradient (primary active transport) 2) Using the Na+ gradient, glucose is transported into the cell via the SGLT-Na+ glucose co-transporter (secondary active transport) 3) Glucose is transported across the basal membrane by the GLUT transporter (facilitated diffusion)