Cellular Interactions and Cell Membrne Transport (L2)

extracellular environment

• everything located outside of the cells

• cells receive nourishment from and release waste

• cells communicate by secreting chemical regaulators into this space

• impprtant for cell survival and communication

EMC: extracellular matrix

• where cells that make up tissues/organs are embedded

• made up of protein fibers (collagen, elastin, etc), ground substances and integrins

• equally as important for cell survival

proteoglycan

• protein-sugar molecules in extracellular matrix

• provide structural support

• retain water

• help regulate cell signaling

actin

• protein that froms microfilaments in cytoskeleton

• maintains cell shape

• support movement

• enable muscle contraction

integrin

• transmembrane receptor proteins

• connect cells to extracellular matrix and cytoskeleton

• regulate cell movement

• tissue repair

• immune response

elastin

• elastic protein in ECM
  allows tissues to stretch and return to their original shape

• provides flexibiity and recoil

• lungs and blood vessels

body fluids and compartments

• made up of fluid - filled compartments

• separated by epithelial cell layers (cell membranes)

• transport occurs between intracellular (jnside) and extracellular (outside) compartments across the plasma membrane

water

• most abunant substance in body

• solvent for molecules

  • small molecules: inorganic ions, sugars, AA

  • large molecules: proteins

• compartmentalized in the body

• not distributed evenlt throughout/distinct fluid spaces = appropriate fluid balance

body fluid compartments

• total body water (TBW)

• extracellular fluid (ECF)

• intertsitial fluid (ISF)

• intracellular fluid (ECF)

• Blood plamsa

total body water (TBW)

• ~60% of body weight

Extracellular fluid (ECF)

• fluid outsde the cells

• 33% TBW

• few proteins, Na⁺ rich

• divides into two groups

  • intertsital fluid

  • blood plasma

intertsitial fluid (ISF)

• ~80% of ECF

• few proteins

blood plamsa

• liquid matrix of blood

• ~20% of ECF

• protein rich

intracellular fluid (ICF)

• fluid with cells

• ~67% of TBW

• mant proteins, K⁺ rich

• support cellular metabolism

epithelial cells

• thin layer of cells coverihng body surfaces

• linng of intrnal organs and cavities

• protective barrier

• absorption ad secretion

• movement accross tissues

endothelial cells

• specialized typed of epithelial cell

• lines inside of blood vessels and lymphatic vessels

• blood stream and surrounding tissues

enterocytes

• specialized epithelial cell

• small intenstine that absorb nutrients

what moves easily across the plasma membrane

• non polar hydrophobic molecules

• small uncharged polar moleucules

what has difficulty moving across the plasma membrane

• large polar molecules

• ions (bc they are charged)

plamsa membrane movement

• depends on size, charge andn polarity

• selectievly permeable = regulates what goes inside and outside

Passive transport characteristics + types

Characteristics:

• spontaneous: no need to be triggred, w/out assistance, only simple diffusion

• no cell energy required (no ATP)

• “downhill” movement: high conc. to low conc.

• when conc. are same on inside and outside = net movement stops

Types:

1. simple diffusion

2. osmosis

3. facilitated diffusion

   1. channel-mediated

   2. carrier-mediated

simple diffusion

• type of passive transport

• random mixing of particles from one location to another

• move through phospholipid bilayer on their own bc of particles’ random statem of motion

• net movement from higher solute concentration to lower solute concentration

  • movement occurs in both drections but net movement = net diffusion

    • diffusion not reuqire membrane

diffusion

• occurs w/out physical seperation of accross a permeable membrane

mean diffusion time

• average time it talkes for a solute to diffuse

• increased w the square of a distance the solutre must travel

  • less distance = faster

  • distances > 100um = too long for diffusion to be effective

    • why the body develop circulation system; rapid transport

diffusion through the plasma membrane

• small non-polar (uncharged) lipid soluable molecules pass easily

  • O₂, steroid hormones, CO₂, urea m ethanol

  • gas exchange: net diffusion of O₂ into cells and CO₂ out of cells due to conc. gradent

• charged ions can pass via ion channels

• large polar molecules cant calss via diffusion = need special carrier protiens (ie: glucose)

factors affecting rates of diffusion

1. magnitude of driving force

2. membrane surface area

3. membrane permeability

4. temperature

magnitude of driving force

• rate of transport directly related to size of driving force

• larger concentration gradient, faster diffusion

• for charged substances: larger electrochemical gradient, faster diffusion

membrane surface area

• directly proportional to rate of transport/diffusion

• larger surface area, faster rate of diffusion: more can travel simultaneously

  • microvili: increase surface area in small intestine to increase nutrient absorption

membrane permeability

• depends of properties of transported substance and proterties of membrane

• highly soluable = more competative than low solubility

temperature

• higher temperature = increasesrate

• molecular E_k (molecular physics)

osmosis

• passive transport

• passage fo water through plasma membrane

• water molecules are uncharged, pass through plasma membrane slowly

• aided by aquaporins (membrane channels

  • many found in kidneys, eyes, lungs, salivary glands, brain

    • wherever large scale H₂O movement is necessary

requirements of osmosis

• solute concentration difference on either side of a membrane permeable to water

• membrane must be impermeable to the solute, or the concentration difference will not be maintained (CRITICAL)

  • solutes that cannot cross and permits osmosis = osmotically active

    • proteins w/in blood plasma

    • large = cannot cross capillaries = active

net movement of water

• from more dilute side to less dilute side

• low solute = more water

• more solute = less water

• area of low wolute conc. to high solute conc.

aquaporins

• in plasma membrane

• permit osmosis

• permament in some membranes but inserted in other membranes in response to regulatory molecules

• without them no H₂O movement to meet physological demands

• 13 types in human body

• some transport water only, some transport small solutes (glycerol)

  • ie: aquagluceroporins, super-aquaporins (distinct structural and functional properties)

• THINK: where are specific types of aquaporins abundant: water managememt in tissues

facilitaed diffusion: channel-mediated transport

• requires transmembrane protein, functions like a passageway or pore

• substance specific (physical and chemical properties)

• some channels are always open, some are gated

• most membranhannels are ion channels

• most are selective for K⁺ and Cl^-, less for Na⁺ and Ca⁺

  • generate electrical signals for neurons or muscles

leak channels

• always open

voltage - gated channels

• voltage changes

ligand-gated channels

• ligen binding

mechanically gated channels

• mecahnical stimuli

carrier mediated transport

• passive transport through carrier

• powered via random movement of molecules, no ATP

• high to low concentration

• requires specific carrier - mediated proteins (permiases)

• transport proteins may always exist in plamsa membrane or be inserted when needed

transport proteins

• conformational shape change from protein

• revolving door (shape has changed still)

• protein changed shape to bind and transport protein

proprties of carrier-mediated transport

• specificity

• competition

• saturation

• all 3 = used in physiological and pharmological data

• all 3 = significant physiological consequences

• compare to

  • diffusion of non polar molecules (none or the properties)

  • diffusion through channels (only specificity)

specificity

• transport only by partiular molecule (lock&key)

competition

• 2 structurally similar molecules compete for carrier

• rate of transport decreases in presence of other molecule

saturation

• number of carriers is finite and reached T_m : transport maximum (plateau)

active transport

• movement of ions and molecules againts their conc. gradient

• nonspontaeous: requires celle energy

• movement is “uphill”: energetically unfavourable

• involves a pump: drives molecules into a direction they dont typically move

• both primary (ATP) and secondary active transport

Primary active transport: Ca²⁺ pump

• located on all cells + ER of triated miscle cells (skeletal and cardiac)

• removed Ca² from cytoplasm by pumping it into the extracellular fluid or cisternae of ER

  • kept atlow levels bc powerful signaling molecule

• creates strong conc. gradient for rapid movement of Ca²⁺ back into cell

  • w/out rapid movement, processes cannot happen properly

• aids release of neurtransmitters in neurons adn in muscle contraction

Primary Active Transport: Na⁺/K⁺ Pump + 3 functions

• found in all body cells

• ATpase enzyme pumos 3 Na⁺ out of the cell and 2 K⁺ into the cell

• serves three functions

• works in an alternating cycle: pump can perfrom work against both conc. gradients simultaneously

1. provides energy for coupled transport of other molecules

2. produces electrichemical impulses in neuron and muscle cells (action potential)

3. maintains osmolality

   1. total solute conc. w/in cell prevents cells from swelling or shrivalling bc of osmotic imbalance

active secondary transport

• AKA coupled transport

• uses electrochemical graduent or concentration gradient previously created by primary active transport (uphill from pump is used)

• involved 2+ molecules or ions

cotransport

if both colecules in secondary active transport are moved in the same direction

countertransport (antiporters)

if one molecule or ion in secondarycative transport is moved in the opporite direction relative to the other one

cotranport of sodium and glucose via sodium-glucose transporters

• SGLT

• hydrolysis of ATP by Na⁺/K⁺ pump maintains low intracellular Na⁺ concentrations

• Na⁺ concentration is higher on one side and glucose concentration is higher on the other, glucose moves up its conc. gradient and Na⁺ moves down its conc. gradient

  • Na⁺ makes strong enough gradient to pull glucose in opposite direction that doesnt follow the gradient

sodium-progton exchange

• antiporter uses e^_ from inward sodium flux

  • regulates intercellular pH → kidney and cardiac muscle

active -passive cooridnation

• ICF/ECF composition differs and ICF composition remains relatively steady

• intracellular concentrations dont change because of continuous balance between creating gradients + active/passive pumps, opposite actions = homeostatis (negtive feedback)

endocytosis

• movement of large molecules such as cholesterol into the cell

• engulfed into a portion of the plasma membrtane, pinch off to form an intracellular vessicle

• 3 types:

  • phagocytosis

  • pinocytosis

  • receptor mediated endocytosis

phagocytosis

• cell eating

• organic fragments, bacteria, particulate

• dead cell debris, destroyed pathogens, immune cells

pinocytosis

• cell drinking

• substance is liquid

• small droplets, dissolved solutesm sample extracellular movemejnt

receptor mediated endocytosis

• low density lipoprotein

• most selective type, ligens bind to receptors on the receptor surface

• receptors exist in a pit. when molecule binds, pit splits off

exocytosis

• large molecules, proteims, hormones, neurotransmitters are secreted

• involves fusion of a vesicle w/ the plasma membrane

• requires ATP (energy input)

• things that are created w/in the cell but must eb trabsported outside to fullfill role: insulin, neurons , glucose,