Interactions Between Cells & the Extracellular Environment Chapter 6 CHEMICAL REGULATORS extracellular environment represents all constituents outside the cell Mechanism of chemical regulators. obtain nourishment, release secretions, eliminate wastes impact/interact neighboring (1) cells, (2) different tissues &/or (3) different organs

Body Fluids Divided into compartments: extracellular 33% bld plasma & interstitial fluid intracellular 67% fluids serve as communication link – cells  tissues  organs One big communication network

connective tissue of a tissue/organ Extracellular Matrix complex network of proteins specific for any given tissue EC fluid interspersed within functions: scaffolding for cellular attachment transmits information to regulate activity, migration, growth & differentiation ECM Outside of the cell connective tissue of a tissue/organ

An Example ECM composed of fibrous proteins but also ground substance, analogous to a hydrated gel & location of IF comprised of glycoproteins & proteoglycans  gel binds water highly functional, complex organization of molecules chemically linked to EC protein fibers & glycoproteins of glycocalyx Location of interstitial fluid Glycocalyx == carbohydrate (sugary) region outside of the ECM Binds water (water loving) forms gel Integrin  class of glycoproteins that extend from the cytoskeleton within the cell. Connect intracellular and various elements of the ECM. Links ECM and ICM components. Allows for info to be exchanged between block integrin - binding site on platelets, slows bld clotting integrins - adhesion molecule between cell & ECM, physically joining EC & IC compartments serve to relay signals or integrate them

Transport Across the Plasma Membrane serves as a “barrier” to movement - EC & IC compartments selectively permeable membrane transport processes E requirements passive transport active transport carrier-mediated transport versus transport without a carrier Selective  only certain things can pass through – can change according to the needs of cells. Can either diffuse across or need a carrier molecule

Diffusion & Osmosis molecules of a solution are in constant motion solvent solute mean diffusion time conc gradient exists, motion tends to eliminate the difference, with the random motion of molecules is diffusion will move in both directions but a net movement from higher to lower until equilibrium is reached Net flux of invt depending upon concentration gradient 100 micrometers is the magic number, this distance or less. PM is 10 nanometers Diffusion times (10^-7 seconds) Time it takes from start to end of diffusion- mean diffusion times Compartment one has higher solute concentration, if membrane is permeable to solute it is going to flow along conc. Gradient Most cells are going to be within 100 um to a capillary, Why in regards to a capillary? – site of exchange, blood in capillary, and nutrients and oxygen and etc in blood. Epithelial tissue is not vascularized so needs to be in this distance in order to obtain the nutrients they need to grow and to get rid of waste. increases with distance; distances kept within 100 μm for effective exchange

will follow concentration gradient between compartments Diffusion through a PM nonpolar molecules  O2 & steroids, or small polar covalent molecules without charge  CO2, ethanol & urea, can easily cross the PM will follow concentration gradient between compartments Within the cell, O2 is low but outside of the cell it is high, so O2 will diffuse into the cell, because cell is metabolically active and contains CO2, the CO2 goes out and is later picked up.

Membrane Channels charged inorganic ions, Na+ & K+, utilize channels Why? Gives you a mechanism for control, REGULATOR. Can be open by particular physiological stimuli. channels may be OPEN or GATED for large, polar molecules, carrier proteins are needed in the PM for movement particular physiological stimuli opens/closes gate

Rate of Diffusion J = PA (Co – Ci) magnitude of conc gradient speed of diffusion per unit time J = PA (Co – Ci) net flow (J) is directly proportional to the conc gradient (Co-Ci), the surface area (A) and the membrane permeability coefficient (P) magnitude of conc gradient diffusing substance’s permeability to PM temperature SA available distance Larger conc gradient => FASTER movement More permeable = faster movement across PM Higher temp = faster diffusion More SA = can move more molecules across that space, increases diffusion Distance, need to watch parameter (100 um) Permeability is very important in how things move across a plasma membrane ** greater P, larger the J across the PM for any given conc difference & A magnitude of conc gradient driving force for diffusion BUT will not move if PM not permeable to that molecule

Osmosis net diffusion of water requirements: follows waters conc gradient requirements: conc difference of solute between sides of membrane membrane selectively impermeable to solute nonpenetrating solute osmotically active creates osmotic pressure “pull” of water aquaporins – water channels facilitate movement of water present in some cell types or can be inserted in response to regulatory molecules Example : solute can’t make it across (non-penetrating solute) In order for water to move it’s going to follow it’s concentration gradient, which depends on how much solute is there More water on outside so flows into where most solute is and makes the inner circle expand. Water can also diffuse through PM without using an aquaporin but depends on pm of the cell

Osmotic Pressure (OP) Inside cell SWELLS Osmotic Pressure- how much pressure do I need to apply so that water does not flow? Higher pressure with 360g/L sucrose  more solutes, greater conc difference, so need to apply more pressure so water does not flow. OP of a sol’n represents the pressure that must be applied to a solution to prevent the net flow of water indicates how strongly a sol’n draws water water drawn more rapidly with greater solute conc

ratio of solute to solvent not completely specified amt of water changes due to MW of substance MOLARITY Molarity vs Molality better measurement of concentration when discussing osmosis weigh one mole of substance and place in 1Kg water thus can compare between solutes since both in same amt of water Molarity: 1.0 mole of solute and bring it up to 1L. 1 mole of glucose = 180 g Molality: 1.0 mole of molecultes, but put into 1kg of H2O, so you end up with slightly different volumes Molarity(M): ratio of solute to solvent, the amount of water changes due to MW of substance Molality (m): both solutes are in the same amount of water. MOLALITY

Osmolality OP depends on ratio of solute to solvent, not chemical characteristics of solute osmolality – Osm total molality of a solution what about electrolytes? ionize plasma & other biological fluids have a complex osmolality due to the presence of organic molecules & electrolytes cell activity leads to constant change Electrolytes dissociate/ ionize -going to have osmosis occurring bc two conc are different Complex bc have organic molecules and cells are constantly changing so needs to be addressed by the organism Isotonic when have same inside and out Cells are dynamic, making and using things-> environment inside and outside cell is constantly changing

Tonicity describes effect of solution on osmotic movement of water, thus cell shape & volume solute load – 300 mOsm solutions described by how they change cell volume (& thus shape) by causing water movement take into account both solute conc & solute permeability for each solute crossing the PM Standard is 300 mOsm -isotonic have no exchange -hypotonic when water moves into cell and becomes lg and round -hypertonic when cell shrinks, loses water If 200 then hypotonic and if 400 then hypertonic

Osmolality vs Tonicity Can a solution be iso-osmotic but not isotonic? YES, if solute is permeable to membrane, ie is a penetrating molecule, thus can freely cross the PM Urea is going to move into the cell and cause fluid flow but have a penetrating molecule * Look if it is penetrating and can or cannot move

Question When a cell comes in contact with a sol’n, hypertonic or hypotonic, the initial conc of solutes determines the degree of change • - impermeant If a cell were placed in a solution containing 100 mOsm impermeant solutes, how would its final volume compare to its initial volume? answer on notecard It would increase by 3 times

Homeostasis of Plasma Concentration variety of mechanisms exist to keep blood plasma osmolality maintained within very narrow limits In kidneys is going to open up water channels and allow us to have water intake

Carrier-Mediated Transport cellular metabolism relies on the cell’s ability to uptake molecules it needs from the EC fluid many of these molecules cannot be attained by simple diffusion, require protein carriers specificity, saturation & competition Comparison Need protein carriers-> and display characteristic of saturation- are carrier mediated If only have 25 carriers then completely saturated at 25 * With diffusion it will continue to move as long as there is a conc gradient carrier proteins display the characteristic of saturation if carrier can transport more one molecule type, then they will compete for transport becomes saturated

Facilitated Diffusion passive transport Display specificity, competition, and saturation depending on carrier We can add transporters to pm or also take them away ** about meeting needs of cell cell stimulated, insert carriers into PM to meet cell needs display specificity, competition & saturation

Active Transport Primary energy required for carrier function typically, molecules/ions moved against their conc gradient process: binding of molecule to be transported to “recognition site” binding stimulates ATP hydrolysis phosphorylation causes carrier protein to undergo conformational change hingelike motion of carrier protein releases transported molecule to other side often referred to as pumps ATP hydrolysis-> energy Pumps- active transport mech (pump utilizing energy)

Na-K Pump creates steep ion gradient functions: provides E for coupled transport of other molecules used to generate electrochemical events (impulse) in nervous & muscle tissue Na movement impt for osmotic reasons stops, observe Nai, cause osmotic influx of water (damage cell) Move Na out and K in

Active Transport Secondary sets up gradient X driven indirectly by passive ion gradients created by operation of primary active pump symport Na wants to move into cell and K wants to move out Symport- when glucose and Na move in same position If molecules moving in opposite direction then anti symport Stop pumping Na-K which means that we are going to lose the concen gradient-> will be able to move for a little while but will eventually stop what happens if the Na-K pump is poisoned?

Movement of solutes across a typical PM involving membrane proteins Many of these membrane proteins can be modulated by various signals, resulting in controlled rise or fall in specific solute fluxes across PM Can move many things like amino acids, NaCl Specialized cells may contain additional transporters and channels

Transport Across Epithelial Membranes ♦ Since epithelial cells line the body’s surface as well as cavities of hollow organs, molecules entering the body must pass through an epithelial cell layer absorption reabsorption transcellular transport, transepithelial transport, transcytosis paracellular transport ♦ Junctional complex that seal off epith but are NOT absolute * directionality* NOTICE polarity, or definite direction of transport in epithelial cells apical - basolateral Movement of Glucose

presence & number dependent on location Junctional Complex physically join presence & number dependent on location “glued” together “velcroed” together

Bulk Transport endocytotic events for secretion, use exocytosis exocytosis can use pinocytosis, phagocytosis, bringing elements/ food into cell or can be very specific through a receptor endocytotic events for secretion, use exocytosis movement of molecules too large to be transport through PM