ForewordForeword

In the course of three months - our staffIn the course of three months - our staff will guide you through the secrets of Me-will guide you through the secrets of Me- - dical Biophysics Both - dical Biophysics Both lectureslectures, and , and practicalspracticals are are obligatory obligatory for students.for students. You will attend Lectures and Practicals You will attend Lectures and Practicals according to timetable (your questions according to timetable (your questions e.g. how to get credit, substitution in the e.g. how to get credit, substitution in the case of illness, etc. are discussed with case of illness, etc. are discussed with teachers during Practical teachers during Practical sessions ) For Instructions to organization of study For Instructions to organization of study and details ask following teachers:and details ask following teachers:Prof. Jakuš - headProf. Jakuš - head, , Dr. Simera-viceheadDr. Simera-vicehead Dr Poliacek-Assoc.ProfDr Poliacek-Assoc.Prof

Content of studyContent of study Covers following topicsCovers following topics .:.: Biophysics of Cell, Biophysics of Cell,

Transport membrane mechanisms, Resting and Transport membrane mechanisms, Resting and Action potentials , Muscle contraction, Synapse, Action potentials , Muscle contraction, Synapse, Basics of respiration, Heart and circulatory sys-Basics of respiration, Heart and circulatory sys-ems, Senses, Hearing, Vision. Changes in body ems, Senses, Hearing, Vision. Changes in body due to action of mechanical an electromagnetic due to action of mechanical an electromagnetic influences, Effects of Sound, Infrared and Ultravio-influences, Effects of Sound, Infrared and Ultravio-let radiations, Radioactivity, Diagnostic methods let radiations, Radioactivity, Diagnostic methods in human medicine: X-ray, Utrasound, Computer in human medicine: X-ray, Utrasound, Computer tomography, Magnetictomography, Magnetic tomography, etc. Therapy tomography, etc. Therapy in human medicine, Biocybernetics, Modern in human medicine, Biocybernetics, Modern Machines, Nanotechnology and many others. Machines, Nanotechnology and many others.

For more detailsFor more details look for my look for my Lectures Lectures being being available to see and download from our faculty available to see and download from our faculty homepage: homepage:

www.jfmed.uniba.sk/index.php?id=3649www.jfmed.uniba.sk/index.php?id=3649

Study Literature - SourceStudy Literature - Source 11..LecturesLectures – – thethe content results from Professors content results from Professors

experience, also from experience, also from Textbook of Medical Textbook of Medical BiophysicsBiophysics (in Slovak (in Slovak )), also from , also from Ganong´s Ganong´s Textbook of PhysiologyTextbook of Physiology

Content of some Lectures and Practicals ,Programme Content of some Lectures and Practicals ,Programme of Lectures, Requirements and condition how to of Lectures, Requirements and condition how to obtain credits, points etc. are available on obtain credits, points etc. are available on web.page: web.page: www.jfmed.uniba.sk/index.php?id=3649www.jfmed.uniba.sk/index.php?id=3649

22..TextbooksTextbooks- - Nave Nave && Nave Nave: Physics for Health : Physics for Health Sciences,1985, Sciences,1985, Ronto,Tarjan et al.:Ronto,Tarjan et al.:An introduction to An introduction to Biophysics with Medical Orientation, 1999,Biophysics with Medical Orientation, 1999,

3. 3. BookletBooklet-- Kukurova etKukurova et al.: al.:BiophysicalBiophysical Elixir, 1991Elixir, 1991

4. 4. WorksheetWorksheet for Practicals for Practicals Jakus,Poliacek, Jakus,Poliacek, SimeraSimera : :Practical Tasks in Medical Biophysics ,2013Practical Tasks in Medical Biophysics ,2013 , it , it contains theory and personal protocol to particular tasks.contains theory and personal protocol to particular tasks.

Medical Biophysics. Biophysics of a Cell. Transport membrane mechanisms. Resting

membrane potential.

LECTURE 1LECTURE 1

Ján Jakuš

(www.jfmed.uniba.sk/index.php?id=3649(www.jfmed.uniba.sk/index.php?id=3649))

Martin 2014

Medical Biophysics

is an interdisciplinary subject of medical scien-is an interdisciplinary subject of medical scien-ces,explaining basic problems of a human body ces,explaining basic problems of a human body at a level of atoms, molecules, cells, tissues, at a level of atoms, molecules, cells, tissues, and organsand organs

answers the physical problems that appear in answers the physical problems that appear in

biology, chemistry, anatomy, physiology...biology, chemistry, anatomy, physiology...

explains effects of radiation, giving rules and explains effects of radiation, giving rules and recommendations for their use and safetyrecommendations for their use and safety

explains and creates new methods and devices explains and creates new methods and devices for diagnosis and treatment of human diseasesfor diagnosis and treatment of human diseases

Medical Biophysics - kind of Medicine

Science, a part of Biophysicsa part of Biophysics

HUMAN CELLDefinitionDefinition: : Cell is a basic anatomical Cell is a basic anatomical

and functional unit of the body with and functional unit of the body with total number of 60.000 bilions and size total number of 60.000 bilions and size from 4-120 from 4-120 µµm (10m (10-6 -6 mm)). . NumberNumber of of cells cells composes composes tissuestissues (206 bones ,600 (206 bones ,600 muscles, thousands of nerves muscles, thousands of nerves )), number of , number of tissues builds tissues builds organs (heart, lungs, organs (heart, lungs, kidney.. kidney.. ))

Typical signs of living cellTypical signs of living cell: : own meta-own meta-bolism, excitability, reproductionbolism, excitability, reproduction

Composition: Cytoskeleton -Composition: Cytoskeleton -surface surface membranemembrane,,cytoplasm,cytoplasm, organellesorganelles ((for for details see our videos at Practical Sessions details see our videos at Practical Sessions also look a book of Biologyalso look a book of Biology))

SURFACE MEMBRANE

SurfaceSurface Membrane of RBC

Surface Membrane (SM) Intracellular SM-Intracellular SM- covers subcellular structures covers subcellular structures

(e.g.Nucleus, Golgi complex, Mitochondria)(e.g.Nucleus, Golgi complex, Mitochondria)Plasmatic SMPlasmatic SM - - covers the surface of each cell covers the surface of each cell

FunctionsFunctions:: semipermeability,semipermeability, division, protec-tion, division, protec-tion, integrative roles, transport of ions, source of integrative roles, transport of ions, source of

enzymes, storage of electric charges, etc.enzymes, storage of electric charges, etc.CompositionComposition: : SM is SM is Phospholipid bilayerPhospholipid bilayer- 45- 45%% Hydrophilic headsHydrophilic heads (consisting of (consisting of phosphates-phosphates-

soluble in watersoluble in water))Hydrophobic tails Hydrophobic tails (consisiting of (consisiting of hydrocarbon hydrocarbon

fatty acidsfatty acids-insoluble in water- 45%-insoluble in water- 45%)) . . Proteins Proteins bilayer (peripheral, integralbilayer (peripheral, integral) ) - 50- 50%% , , ++ Sugar + Sugar + Cholesterol Cholesterol (5(5%)%)

HeadsHeads are (are (+) electrically charged+) electrically charged and directed and directed towards the membrane exterior, towards the membrane exterior, tails tails are are charged charged negatively (–), being oriented to membrane interiornegatively (–), being oriented to membrane interior

Transport Membrane Mechanisms are responsible for movement of water and are responsible for movement of water and

solutes across the cell membranesolutes across the cell membraneare of vital importance for cell metabo-are of vital importance for cell metabo-

lism, for production of cell electricity i.e. lism, for production of cell electricity i.e. (resting and action membrane potentials)(resting and action membrane potentials)

Types: Types: PASSIVEPASSIVE - it does not need deli- - it does not need deli-very of a free energy. very of a free energy. (Simple and Facilita-(Simple and Facilita-ted Diffusion, Osmosis, Filtrationted Diffusion, Osmosis, Filtration))..

ACTIVE ACTIVE - - free energy from ATP is free energy from ATP is needed and must be delivered needed and must be delivered (Na-Kpump, (Na-Kpump, Ca-pump, H-pump, exo/ endo-cytosis, and Ca-pump, H-pump, exo/ endo-cytosis, and phagocytosisphagocytosis))

Simple Diffusion through cell membrane through cell membrane

Simple DiffusionSimple Diffusion is a kind of passive membrane transport of is a kind of passive membrane transport of

HH220, solutes, or gases 0, solutes, or gases (O(O22, CO, CO22)) from the space from the space with a higher concentration towards the space with a higher concentration towards the space with lower one (along the concentration gra-with lower one (along the concentration gra-dientdient)), untill the equilibrium is established. , untill the equilibrium is established. Total volume of solution does not change in Total volume of solution does not change in both of spaces.both of spaces.

Rate of diffusionRate of diffusion:Fick Law: :Fick Law: J = - d . conc.J = - d . conc.ggrad.rad. [[d- koeficient of diffusiond- koeficient of diffusion]]

Generally:Generally: diffusion depends diffusion depends - - linearlylinearly on a on a conc. gradient, solubility of a matter, and on conc. gradient, solubility of a matter, and on ambient temperatureambient temperature NonlinearlyNonlinearly dependsdepends on a size of particleson a size of particles

Types of diffusionTypes of diffusion: Simple, Facilitated, Throu-: Simple, Facilitated, Throu-gh the protein channels gh the protein channels

Scheme of Facilitated DiffusionScheme of Facilitated Diffusion

Facilitated DiffusionFacilitated Diffusion

is a passive transport mechanism of bigger is a passive transport mechanism of bigger molecules (e.g.aminoacidsmolecules (e.g.aminoacids)),along a ,along a concentration gradient, when substance concentration gradient, when substance binds to a binds to a protein carrierprotein carrier

thethe carrier iscarrier is protein protein placed within the placed within the membrane and undergoes a process of membrane and undergoes a process of conformation conformation (is a change of its (is a change of its chemistrychemistry))

afterafter bindingbinding of molecule of molecule and and conformation,conformation, the carrier shifts (turns the carrier shifts (turns around around )) and finally releases substance and finally releases substance on an opposite site of a cell membraneon an opposite site of a cell membrane

Diffusion through the protein (ion Diffusion through the protein (ion selective selective)) channels channels

is a is a passive transportpassive transport of ions Na of ions Na++, K, K++, Ca, Ca2+2+, , ClCl- - ,or low molecular soluble sub-stances ,or low molecular soluble sub-stances through the protein channels within the through the protein channels within the membrane, along the concen-tration gradient membrane, along the concen-tration gradient

Protein channels are :1.Protein channels are :1.“voltage“gated “voltage“gated --

they are open or closed (gatingthey are open or closed (gating)) due to due to

a membrane electricity,a membrane electricity,or 2.or 2.„ligand“gated„ligand“gated--when e.g. a hormone binds to a channel, when e.g. a hormone binds to a channel, thus opening it.thus opening it.

„ „Voltage“ and „ligand“ gated protein Voltage“ and „ligand“ gated protein

(ion selective (ion selective)) channels channels

FiltrationFiltration

is a passive transport of water and small is a passive transport of water and small particles from a space with higher particles from a space with higher hyd-hyd-rostatic pressurerostatic pressure to a space with lower to a space with lower oneone

the power that drives Filtration is the power that drives Filtration is Pressure gradient Pressure gradient of aof a hydrostatic hydrostatic pressurepressure (not a concentration gradient ! (not a concentration gradient ! ))

examplesexamples: filtration and resorption in : filtration and resorption in capillary loop or in kidneyscapillary loop or in kidneys

OsmosisOsmosisis kind of passive transport through the is kind of passive transport through the

semipermeable cell membrane, when semipermeable cell membrane, when only wateronly water moves from a space with lower concentration moves from a space with lower concentration (lower osmotic pressure(lower osmotic pressure)) to a space with higher to a space with higher concentration (higher osmotic pressureconcentration (higher osmotic pressure)), till to , till to equilibrium.Total volume of solution in both equilibrium.Total volume of solution in both compartments will change. compartments will change.

Simply –water wants to dilute more concentrated Simply –water wants to dilute more concentrated solutionsolution (Van Hoff´s Law(Van Hoff´s Law))

normal osmolaritynormal osmolarity 300 mOsm300 mOsm//l- l- isotonic isotonic solutionsolution with blood plasma (e.g. 0.9 % NaCl, or with blood plasma (e.g. 0.9 % NaCl, or 5% of glucose5% of glucose)) Below 0.9%- Below 0.9%- hypotonic solutionhypotonic solution

Above 0.9% - Above 0.9% - hypertonic solutionhypertonic solution exampleexample: Osmotic fragility of RBC ( see : Osmotic fragility of RBC ( see practicals practicals ))

OSMOSIS – schemeOSMOSIS – scheme

Changes in size of RBC due to osmosisChanges in size of RBC due to osmosis (HAEMOLYSIS)(HAEMOLYSIS)

ACTIVE MEMBRANE TRANSPORTS

transport of molecules among cells against the concentration, or electric gradients,

a a delivery of free energy from ATP is crucial.delivery of free energy from ATP is crucial.

ClassificationClassification:: Primary active transportPrimary active transport through the through the selectíve ions channels. Pumps : Na +- K+ pump (in all cells), Ca 2+- pump (in muscle cells), H+- proton pump (in cells of stomach producing HCl)

Secondary active transportSecondary active transport when a substance (e.g. glucose) binds on ion (Na+),

then this complex (Na+ glucose) is carried through the membrane actively (the glucose-Naglucose-Na++ contransport contransport)), , exo-/endo, phagocytosisexo-/endo, phagocytosis

NaNa++-K-K++ pump pump (Na(Na++- K- K++ ATPase ATPase))

NaNa++- K- K++ pump – scheme pump – scheme

NaNa++-K-K+ + pump pump (Na(Na++- K- K++- ATP-ase- ATP-ase))

- - It isIt is anan enzyme enzyme,, placed within the placed within the cell membranecell membrane (number =10 (number =106 6 molecules withinmolecules within a membrane of a membrane of one one neuron neuron ))

- it carries - it carries 3 ions of Na3 ions of Na++ from inside to from inside to outside, and at the same time, outside, and at the same time, 2 K2 K++ from from outside to inside of the celloutside to inside of the cell

- It can exchange max. 200 NaIt can exchange max. 200 Na++ and 133 K and 133 K++ / sec. (maximal capacity of pump)/ sec. (maximal capacity of pump)

- It requires delivery of - It requires delivery of free energyfree energy (from (from ATPATP))

- It is important for renewal of electric It is important for renewal of electric charges on body cellscharges on body cells

Exocytosis, Endocytosis Exocytosis, Endocytosis (Phagocytosis (Phagocytosis))

ACTIVE membrane transports.: ACTIVE membrane transports.: Exocytosis and Endocytosis.Exocytosis and Endocytosis.

ExocytosisExocytosis - “ - “cell vomiting“ is a is a release of larger molecules by the release of larger molecules by the protrusion of a cellular membrane, protrusion of a cellular membrane, under delivery of energy and Caunder delivery of energy and Ca2+2+ ions ions

Endocytosis Endocytosis –“cell eating“ is an is an uptake of molecules by a cellular uptake of molecules by a cellular membrane, e.g. ingestion of bacteria membrane, e.g. ingestion of bacteria by leukocytes by leukocytes (phagocytosis(phagocytosis)). . It needs It needs a delivery of energy, too.a delivery of energy, too.

Resting membrane potential (RMPResting membrane potential (RMP))It is an It is an electric potential differenceelectric potential difference measured measured

between (+) charged cell exterior and (–) between (+) charged cell exterior and (–) charged cell interior. Its value is negative and charged cell interior. Its value is negative and equals to a Sum of equals to a Sum of Equilibrium PotentialsEquilibrium Potentials of of all 3 ions (Kall 3 ions (K++, Na, Na++, Cl, Cl--).).

is a result of membrane is a result of membrane semipermeability semipermeability i.e. i.e. different leakage of cell membrane for 3 main different leakage of cell membrane for 3 main ions (Kions (K++, Na, Na++, Cl, Cl--).).

permeability of cell membrane for ions at permeability of cell membrane for ions at rest is: is:

KK+ + : Na: Na+ + : Cl: Cl-- = 1 : 0.04 : 0.45 = 1 : 0.04 : 0.45 KK+ + : Na: Na+ + : Cl: Cl-- = 100 : 4 : 45 (% = 100 : 4 : 45 (%))Value of RMP for nerve cells is:Value of RMP for nerve cells is: -70 mV -70 mV, ,

sceletal muscle:sceletal muscle:– 90 mV– 90 mV, heart muscle:, heart muscle:- - 80mV80mV, smooth muscle: , smooth muscle: -50 mV-50 mV (non-stabile) (non-stabile)

Equilibrium Potential Equilibrium Potential (EP)(EP) is a value is a value of electrical voltage that just stops the of electrical voltage that just stops the passive diffusion of ions (Kpassive diffusion of ions (K++ ,Na ,Na++ ,Cl ,Cl --)) along along their concentration gradientstheir concentration gradients

CellCell Inside (Inside (--) charged) charged CellCell Outside(+) cha.Outside(+) cha.((because PROTEINS inside) (because Na because Na ++ outside)outside)

Concentration and electrical Concentration and electrical gradients of Kgradients of K++, Na, Na++, Cl, Cl-- ions ions OUTSIDE INSIDEOUTSIDE INSIDE

Nernst formulaNernst formulaEach ion has its own Each ion has its own Equilibrium PotentialEquilibrium Potential (mV) (mV) which can be countedwhich can be counted: : ((Nernst counted it only for KNernst counted it only for K+ ) )

Goldman´s EquationGoldman´s EquationSumation of all Equilibrium potentials (for K, Sumation of all Equilibrium potentials (for K, Na, Cl ) results in a Na, Cl ) results in a real valuereal value of Resting of Resting Membrane Potential ( e.g. V Membrane Potential ( e.g. V mm = -70 mV for = -70 mV for

neuronal cellsneuronal cells)) Goldmann counted it for Goldmann counted it for all 3 ions (their all 3 ions (their concentrations outside and inside) +concentrations outside and inside) + the the permeabilities of permeabilities of membrane for 3 ionsmembrane for 3 ions

for comming and attention

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