Interactions Between Cells and the Extracellular Environment

Compiled and Presented by

Marc Imhotep Cray, M.D.

Basic Medical Sciences Professor

Companion Notes http://www.slideshare.net/drimhotep/ivmsoverview-of-cell-biology

Extracellular Environment

Includes all constituents of the body located outside the cell.

Body fluids are divided into 2 compartments:

Intracellular compartment:

67% of total body H20.

Extracellular compartment:

33% total body H20.

20% of ECF is blood plasma.

80% is interstitial fluid contained in gel-like matrix.

2

Extracellular Matrix

Consists of collagen, elastin and gel-like ground substance. Interstitial fluid exists in the hydrated gel of the ground

substance. Ground substance:

Complex organization of molecules chemically linked to extracellular protein fibers of collagen and elastin, and carbohydrates that cover the outside of the plasma membrane.

Collagen and elastin:

Provide structural strength to connective tissue.

Gel: Composed of glycoproteins and proteoglycans which have a high

content of bound H20 molecules.

Integrins are glycoproteins that serve as adhesion molecules between cells and the extracellular matrix.

3

Categories of Transport Across the Plasma Membrane

Cell membrane is selectively permeable to some molecules and ions. Not permeable to proteins,

nucleic acids, and other molecules.

Mechanisms to transport molecules and ions through the cell membrane: Carrier mediated transport:

Facilitated diffusion and active transport.

Non-carrier mediated transport.

Diffusion and osmosis.

May also be categorized by their energy requirements:

Passive transport:

Net movement down a concentration gradient.

Does not require metabolic energy (ATP).

Active transport:

Net movement against a concentration gradient.

Requires ATP.

4

Diffusion

Molecules/ions are in constant state of random motion due to their thermal energy. Eliminates a concentration gradient and distributes

the molecules uniformly.

Physical process that occurs whenever there is a concentration difference across the membrane and the membrane is permeable to the diffusing substance.

5

Diffusion Through Plasma Membrane

Cell membrane is permeable to:

Non-polar molecules (02).

Lipid soluble molecules (steroids).

Small polar covalent bonds (C02).

H20 (small size, lack charge).

Cell membrane impermeable to:

Large polar molecules (glucose).

Charged inorganic ions (Na+).

6

Rate of Diffusion

Speed at which diffusion occurs. Dependent upon:

The magnitude of concentration gradient.

Driving force of diffusion.

Permeability of the membrane.

Neuronal plasma membrane 20 x more permeable to K+ than Na+.

Temperature.

Higher temperature, faster diffusion rate.

Surface area of the membrane.

Microvilli increase surface area.

7

Osmosis

Net diffusion of H20 across a selectively permeable membrane.

Movement of H20 from a high[H20] to lower [H20] until equilibrium is reached.

2 requirements for osmosis: Must be difference in [solute] on the

2 sides of the membrane.

Membrane must be impermeable to the solute.

Osmotically active solutes: Solutes that cannot pass freely

through the membrane.

8

Effects of Osmosis

H20 moves by osmosis into the lower [H20] until equilibrium is reached (270 g/l glucose).

Osmosis ceases when concentrations are equal on both sides of the membrane.

9

Osmotic Pressure

The force that would have to be exerted to prevent osmosis. The greater the [solute] of solution, the > the osmotic

pressure.

Indicates how strongly the solution “draws” H20 into it by osmosis.

10

Molarity and Molality

One-molar solution: 1 mole of solute dissolved in H20 to = 1 liter.

Exact amount of H20 is not specified.

Ratio of solute to H20 critical to osmosis. More desirable to use molality (1.0 m).

One-molal solution: 1 mole of solute is dissolved in 1 kg H20.

Osmolality (Osm): Total molality of a solution.

Freezing point depression: Measure of the osmolality.

1 mole of solute depresses freezing point of H20 by –1.86oC. Plasma freezes at –0.56oC = 0.3 Osm or 300 mOsm.

11

Effects of Ionization on Osmotic Pressure

NaCl ionizes when dissolved in H20. Forms 1 mole of Na+ and 1 mole of Cl-, thus has a concentration of 2 Osm.

Glucose when dissolved in H20 forms 1 mole, thus has a concentration of 1 Osm.

12

Tonicity

The effect of a solution on the osmotic movement of H20.

Isotonic: Equal tension to plasma.

RBCs will not gain or lose H20.

. RBC will crenate.

Hypotonic:

Osmotically active solutes in a lower osmolality and osmotic pressure than plasma.

RBC will hemolyse.

Hypertonic:

Osmotically active solutes in a higher osmolality and osmotic pressure than plasma

13

Regulation of Blood Osmolality

Maintained in narrow range by regulatory mechanisms.

If a person is dehydrated:

Osmoreceptors stimulate hypothalamus:

ADH released.

Thirst increased.

Negative feedback loop.

14

Carrier-Mediated Transport

Molecules that are too large and polar to diffuse are transported across plasma membrane by protein carriers.

Characteristics of protein carriers: Specificity:

Interact with specific molecule only.

Competition: Molecules with similar

chemical structures compete for carrier site.

Saturation: Tm (transport maximum):

Carrier sites have become saturated.

15

Facilitated Diffusion

Passive: ATP not needed.

Powered by thermal energy of diffusing molecules.

Involves transport of substance through plasma membrane down concentration gradient by carrier proteins.

Transport carriers for glucose designated as GLUT.

16

Primary Active Transport

Hydrolysis of ATP directly required for the function of the carriers.

Molecule or ion binds to “recognition site” on one side of carrier protein.

Binding stimulates phosphorylation (breakdown of ATP) of carrier protein.

Carrier protein undergoes conformational change. Hinge-like motion releases

transported molecules to opposite side of membrane.

17

Na+/K+ Pump

Carrier protein is also an ATP enzyme that converts ATP to ADP and Pi.

Actively extrudes 3 Na+ and transports 2 K+ inward against concentration gradient.

Steep gradient serves 4 functions:

Provides energy for “coupled transport” of other molecules.

Regulates resting calorie expenditure and BMR.

Involvement in electrochemical impulses.

Promotes osmotic flow. 18

Secondary Active Transport

Coupled transport.

Energy needed for “uphill” movement obtained from “downhill” transport of Na+.

Hydrolysis of ATP by Na+/K+ pump required indirectly to maintain [Na+] gradient.

19

Secondary Active Transport

Cotransport (symport):

Molecule or ion moving in the same direction as Na+.

Countertransport (antiport):

Molecule or ion moving in the opposite direction of Na+.

Glucose transport is an example of:

Cotransport.

Primary active transport.

Facilitated diffusion.

20

Transport Across Epithelial Membranes

In order for a molecule or ion to move from the external environment into the blood, it must first pass through an epithelial membrane.

Absorption: Transport of digestion

products across the intestinal epithelium into the blood.

Reabsorption: Transport of molecules out

of the urinary filtrate back into the blood.

Transcellular transport: Moves material through the

cytoplasm of the epithelial cells.

Paracellular transport: Diffusion and osmosis

through the tiny spaces between epithelial cells.

21

Bulk Transport

Movement of many large molecules, that cannot be transported by carriers, at the same time.

Exocytosis:

Fusion of the membrane-bound vesicles that contains cellular products with the plasma membrane.

Endocytosis:

Exocytosis in reverse.

Specific molecules can be taken into the cell because of the interaction of the molecule and protein receptor.

22

Membrane Potential

Difference in charge across the membrane.

Cellular proteins and phosphate groups are negatively charged at cytoplasmic pH. These anions attract

positively charged cations from ECF that can diffuse through the membrane pores.

23

Membrane Potential (continued)

Membrane more permeable to K+ than Na+.

Concentration gradients for Na+ and K+.

K+ accumulates within cell also due to electrical attraction.

Na+/ K+ATPase pump 3 Na+ out for 2 K+ in.

Unequal distribution of charges between the inside and outside of the cell, causes each cell to act as a tiny battery.

24

Equilibrium Potentials

Theoretical voltage produced across the membrane if only 1 ion could diffuse through the membrane.

If membrane only permeable to K+, K+ diffuses until [K+] is at equilibrium. Force of electrical attraction and

diffusion are = and opposite.

At equilibrium, inside of the cell membrane would have a higher [negative charges] than the outside.

Potential difference: Magnitude of difference in charge

on the 2 sides of the membrane.

25

Nernst Equation

Allows theoretical membrane potential to be calculated for particular ion. Membrane potential that would exactly balance the

diffusion gradient and prevent the net movement of a particular ion.

Value depends on the ratio of [ion] on the 2 sides of the membrane.

Ex = 61 log [Xo]

z [Xi] Equilibrium potential for K+ = - 90 mV.

Equilibrium potential for Na+ = + 60 mV.

26

Resting Membrane Potential

Resting membrane potential is less than Ek because some Na+ can also enter the cell.

The slow rate of Na+ efflux is accompanied by slow rate of K+ influx.

Depends upon 2 factors: Ratio of the concentrations of each ion on the 2

sides of the plasma membrane.

Specific permeability of membrane to each different ion.

Resting membrane potential of most cells ranges from - 65 to – 85 mV.

27

Cell Signaling

How cells communicate with each other.

Gap junctions: Signal can directly travel from 1 cell to the next through

fused membrane channels.

Paracrine signaling: Cells within an organ secrete regulatory molecules that

diffuse through the extracellular matrix to nearby target cells.

Synaptic signaling: Means by which neurons regulate their target cells.

Endocrine signaling: Cells of endocrine glands secrete hormones into ECF.

For a target cell to respond to a hormone, NT, or paracrine regulator; it must have specific receptor proteins for these molecules.

28

Cellular Transport

29

Diffusion, Dialysis and Osmosis Tutorial by RM Chute Osmosis - Examples Colorada State University Osmosis by Terry Brown Interactive Cellular Transport by Rodney F. Boyer Hypotonic, Isotonic, Hypertonic by June B. Steinberg Osmosis McGraw-Hill Companies, inc Symport, Anitport, Uniport by University of Wisconsin Facilitated Diffusion by University of Wisconsin Passive and Active Transport from Northland Community and

Technical College The Plasma Membrane Dr JA Miyan at Department of

Biomolecular Sciences, UMIST, UK Endocytosis of an LDL EarthLink Osmosis (thistle tube)

Cellular Structure and Function

30

Comparison of Prokaryote, Animal and Plant Cells by Rodney F. Boyer

Flash animations of Biological Processes by John L. Giannini Organize It by Leif Saul Stem Cells Sumanas Inc. Membrane Structure Tutorial Various Cellular Animations University of Alberta Cellular Receptor Animations University of Oklahoma Cell Tutorial from "Cells Alive!" Simple cell by Terry Brown Kinesin - Molecular Motor Sinauer Associates Inc., W. H. Freeman

Co. and Sumanas Inc. Kinesin Movie RPI Cellular Animations by Donald F. Slish Flagella and Cilia from Northland Community and Technical College