6/10/14 Rad Bio: interactions with matter p. 1 of 85 Illinois Institute of Technology PHYS 561...

6/10/14 Rad Bio: interactions with matter p. 1 of 85

Illinois Institute of Technology

PHYS 561 RADIATION BIOPHYSICS:

Lecture 3:Interaction of Photons with Matter;

Radiation Chemistry;Introduction to BiologyANDREW HOWARD

10 June 2014


Radiation interacts with matter

We’ll investigate the chemical changes that occur in matter, particularly soft tissue, when ionizing radiation impinges on it;

But first we need to finish discussing the initial interactions themselves.


Outline of Session

Left over from chapter 5:– Pair production– Bremsstrahlung– Charged particles &

matter– Interaction of photons

with matter– Size scales and

biological cells– Energy deposition at

different physical scales– Neutrons

Chapter 6:– Types of energy

transfer from electrons– Free Radicals– Radiation Chemistry of

water– Fricke dosimeter– Recombination,

Restitution, Repair

Biology 101


Relevant references Some significant references on photoelectric effect and

the interactions of photons with biological tissue:

1. J.H. Hubbell (1977) Radiation Research 70: 58-81. 2. J.H. Scofield (1973) Theoretical Photoionization

Cross Sections from 1 to 1500 keV, Report UCRL-51326, University of California Lawrence Livermore National Laboratory, National Technical Information Center, Springfield, VA

3. A.M. Kellerer and H.H. Rossi (1971) Radiation Research 47: 15-34

4. H.H. Rossi (1959) Radiation Research 10: 522-531


Typos of the Day

Page 79, first paragraph under “IMPORTANCE OF THE COMPTON PROCESS”, 4th line:“with attention the the” “with attention to the”

Page 86, List of possibilities, #3:“Either M or m0 is at rest” “Both M and m0 are at rest”

Page 87, 2nd paragraph, 1st line:“The four principle” “The four principal”


Pair Production

e- + e+; see fig. 4.7 Can happen if E > 1.022 MeV = 2 * m0(e-)c2

Rapidly increasing cross-section > 1.022 MeV This is the predominant mode of interaction over a

range from a bit above that value up to ~5MeV Stopping power/atom varies as Z2

Energy transferred is h - 1.022 MeV


What pair production does

Scattering nucleus plays fairly passive role– not much momentum transferred to nucleus– but it does soak up some momentum;

otherwise we couldn’t get it to happen at all Generally the positron gets annihilated, giving off a

pair of 0.511 MeV photons. These generally escape and are not part of the absorbed energy


Bremsstrahlung:Radiative Energy Loss

“Braking radiation”:A fast electron loses energy to its environment in a nonspecific way due to Coulombic interaction with neighboring charged particles.

The static particles are much more massive than the electron, so they don’t get accelerated nearly as much as the electron does: but the electron does get accelerated.

What happens when an electron is accelerated? It has to radiate! This type of Coulombically-motivated radiation is Bremsstrahlung


Dependence of Bremsstrahlung on Z High-Z elements have much higher

cross sections for braking radiation for a given initial electron energy because the acceleration goes like Z

Higher electron energies produce more Bremsstrahlung than lower electron energies


Significance of Bremsstrahlung

Example in X-ray generators: 1.5418Å (8KeV) characteristic X-rays are produced

in great quantity when we shoot fast electrons at a copper target: L-to-K shell transition emissions

BUT: we also get a lot of radiative transfer of energy from the electrons as they move past the copper atoms. This gives rise to Bremsstrahlung, which has no characteristic energies.

Thus the spectrum is like this:


Output X-ray Spectrum of a Copper Target


Overview of photon-medium interactions

We’ve seen four mechanisms by which photons can transfer energy to a medium:

Photoelectric effect (mostly below 1MeV) Coherent scattering (mostly below 20 keV) Compton scattering (peaks around 1MeV) Pair production (starts @ 1.022 MeV; dominates at

high energy) We can write the overall event cross-section as

µtot = PE + coh + Compton +pair


What predominates where?

Cf. fig. 5.2(a),(b) For lead, Compton falls off from 100 keV

upward and pair production takes over ~ 5MeV

These figures make the distinction between absorption and transfer as well


How do mixtures absorb?

We’ll come back to this later: Mixtures, including polyatomic

compounds, absorb according to their individual atomic attenuation properties, weighted by their mole fraction


Attenuation Coefficients for Molecules (and mixtures)

Calculate mole fraction fmi for each atom type i in a molecule or mixture:

– subject to ifmi = 1

– That’s why we call these mole fractions

Recognize that, in a molecule, fmi is proportional to the product of the number of atoms of that type in the molecule, ni, and to the atomic weight of that atom, mi:fmi = Qni mi

(Q a constant to be determined)


Attenuation coefficients, concl’d

Thus ifmi = i Qni mi = 1 so Q = (i ni mi)-1

Then (/) for the compound will be(/)Tot = ifmi (/)i = iQni mi(/)i

= (i ni mi)-1 ini mi(/)i

This will, in fact, work even with mixtures of compounds, as long as you keep your mole fractions straight.


Calculating Mole Fractions and Attenuation Coefficients

Example 1: Water (in book):– H2: n1 = 2, m1 = 1; O: n2 = 1, m2 = 16– Q = (i ni mi)-1= (2*1 + 1 * 16)-1 = 1/18– Thus fH2

= 2/18, fO = 16/18,

– (/)Tot = ifmi(/)I = (2/18)*(0.1129cm2g-1) + (16/18)(0.0570 cm2g -1)= 0.0632 cm2g-1

Benzene (C6H6):– C6: n1 = 6, m1 = 12; H6: n2 = 6, m2 = 1– Q = (6*12+6*1) = 1/78, fC6

= 72/78, fH6 = 6/78


Interaction of Charged Particles with Matter

See pages 84 & 85 in the text-Provides solutions to the dynamical equations describing motion of a heavy charged particle past a stationary electron or (by relativity) motion of an electron past a stationary heavy particle: F = kze2/r2 along line MQ

Q


Interaction of e- With Heavy Charged Particle

Momentum imparted to electronat distance of closest approach:

classical coherentscattering by e-:

non relativistic


Interaction of Charged Particles with Matter

Recall diagram 5.3, p.84. The crucial equation is for E(b), the energy

imparted to the light particle: E(b) = z2r0

2m0c4M/(b2E)where E is the (nonrelativistic) kinetic energy of the moving particle = (1/2)Mv2.

It increases with decreasing impact parameter b, which stands to reason

Energy imparted is inversely proportional to the kinetic energy E of the incoming heavy particle!


Why does this formula matter?

Rate of energy loss is inversely proportional to the energy of the incoming particle

So most of the energy is yielded up as the heavy particle approaches its resting state

There are some details we’ve skipped, but they’re readily available in other textbooks.


Relativity tells us this is important! We usually think about the electron moving and the heavy

nucleus being stationary, not the other way around. Why do we go through this derivation?

(a) This could actually happen as described (b) Galilean (or Einsteinian!) relativity says this is equivalent to

what happens if the electron is moving and the heavy particle is at rest. That’s the more typical situation: but the analysis still works.

(c) If M=m0, i.e. an electron-electron interaction, then the assumption of minimal interactivity fails, but we still find that the energy transfer goes like 1/v2 or like 1/E.


Final steps in absorption

Let’s think about a high-energy photon entering a biological medium

It undergoes a modest number of scattering events that give rise to energetic (keV - MeV) electrons

These energetic electrons will themselves only affect the medium once they have transferred energy to other electrons in ~10-50 eV packets

Four mechanisms for doing that:(a) Delta rays (c) Bremsstrahlung in motion(b) Photoelectric (d) Direct collision


Delta rays We expect that each individual event transfers a small amount

of momentum, so the incoming electron doesn’t change direction all that much

There are exceptions: these are delta rays. The “delta ray” is the common name for a secondary electron

that itself has enough energy to ionize other things The ionization events caused by the delta ray can produce

electrons that have energies up to half of that of the primary electron

So some delta rays will even produce tertiary electrons that are themselves delta rays!


Photoelectric processes

If the primary photon is absorbed by an atom, a K or L-shell atomic electron is ejected

This makes an outer-shell electron hop in to fill the inner-shell vacancy, giving rise to an output photon with an energy equal to the difference in shell energies

The photon has to undergo ordinary scattering (probably Compton) in order to transfer energy

This process is most likely in high-Z media, for which the capture cross section is measurable


Bremsstrahlung with movement Caused by Coulombic interaction of an emitted

electron with nucleus Incoming electron decelerates a little due to these

interactions This is not like the 1/E-dependent process we just

described, because not much happens to the target in this instance

Loss due to Bremsstrahlung is important for incoming electrons above 10MeV in lead or 100 MeV in water: that corresponds to almost 200 times the rest energy of the electron


Direct collisions Extreme form of

Bremsstrahlung: electron stops and gives up all its kinetic energy to the absorber

Rare but can be measured

e-


Dose: a definitional reminder

Remember that dose is about deposition (or absorption) of energy per unit mass, while kerma is about transfer of energy per unit mass

So energy that escapes the neighborhood of the initial event may not count in the dose in that region, but rather will count in the dose of some other region

Kerma, by contrast happens at the moment of impact

So kerma can be lower or higher than dose depending on circumstances


Dose and KermaSee Fig. 5.5 in text.

Because secondary events extend farther into tissue (or other) than the initial deposited radiation, dose extends farther into the interior than kerma.


Photons interacting with matter

We mentioned at the beginning of the lecture that the interaction of a high-energy photon with a chunk of matter involves

– Photoelectric effect– Coherent scatter– Compton scatter– Pair production


Compton Scattering, Revisited

The most important of these processes for h > 100 KeV is Compton scatter, especially if the matter is water or tissue

See fig. 5.2(B) in the text to see why:µab/ (Compton) predominates above 100KeV


Compton Processes in Tissue

Biological soft tissue is predominantly made up of H, C, N, O, and a little P and S. So attenuation of photons is dominated by those light elements (Z 16)


Dose

Remember Dose = energy deposited per unit mass.

What is the meaningful size scale for a mammalian cell?

We’ll need to know this to estimate dose on a cell.

size scales 5m

1 g/cm3 for water or soft tissue

mass of (5m)3 =(5 * 10-4cm)3 =125 * 10-12cm3 1g/cm3

=125 * 10-12g = 1.25 * 10-13kg


Energy Absorbed in a Cell

Suppose N Joules of energy are deposited in a 70 kg human. Nominally the dose is N/70 Gy.

How much energy is deposited in a single (5µm)3 cell? (N/70)Gy * 10-13 kg= (N/70)*10-13 J= (1.3*10-15)*N J= [(1.3*10-15)*N]/1.609*10-19 J= 8500*N eV. So it’s a lot of energy!

Is the Bethe-Blocke continuous slowing-down approximation applicable here? No! Too much energy is being stopped per cell for it to be applicable. But we try to use it anyway.


Track structure

We draw different kinds of conclusions depending on the size range we think about

The smaller the target, the bigger the fluctuations in dose that we have to recognize

So deliver of 1 cGy to a large volume could mean we’re delivering anywhere between 0 and 103 Gy to a single chromatin fiber

We can attempt to account for this in various ways; Rossi does it in terms of EY/d


Can LET tell us what we want? Envision variations in dose in terms of the individual

values of E/m for small m; these may differ from the bulk dose by many orders of magnitude

Rossi defines E/m for these small masses as the local energy density, Z

Remember that LET is dEL/dl, where l is the length along the track of the ionization source.

This might give us a handle on the effectiveness of a given bulk dose in causing damage, or it might not.

Rossi uses LET in fudging his values, as we’ll now discuss.


Rossi’s alternative

He makes some assumptions: Particles and their secondaries deposit over

spherical volumes of specific size Source and its secondaries can deposit an

energy Ey within the sphere We call each deposition an event Event size Y is defined as Ey/d, where d is the

sphere diameter The hope is that for idealized tracks, Y will be a

constant independent of d


How this is used

Rossi fudges the real spheres by looking at experimental systems involving spherical ionization chambers containing low-pressure gases;

These become surrogates for tiny tissue-equivalent spheres

Then he plots Y as the independent axis and the energy loss D(Y*), corrected for LET distribution

See fig. 5.6: for 1.5 µm spheres the largest D(Y*) values occur around 70 keV/µm for protons


Local energy density Tissues have densities close to 1 g cm-3 = 103 kg m-3

Alpen shows you that the amount of locally deposited energyZ ~ 30.6 d-2 J kg-1

So for high LET and small d, this can be as high as 10.9 Gy for reasonable values of Y

For high LET radiation lots of events produce Z=0 and a few give us very big values

For low LET is more boring: the distributions are Gaussian and centered on the absorbed dose

General conclusion: high-LET radiation is harder to predict results at the single-cell level


Demonstration That Events Don’t Interact Much

Spurs are 400 nm apart

1 nm = 10-9 m

400 nm = 0.4 m

Hydrogen radical diffusion (see below):

8 10-5cm2s-1 diffusion constant for H•

Typical lifetime 10-6s

Typical diffusion distance = 180 nm

This is smaller than the distance between spurs!


Mozumder & Magee

[1 MeV “typical” electron] Portion of energydeposited

Spurs 6 - 100 eV 65% Blobs 100 - 500 eV 15% Tracks 500 - 5000 eV 20%


Blobs, Spurs, and Tracks:Distribution is Energy-Dependent

Mozumder & Magee: short tracks dominate at low primary electron energy; spurs more important at high energy


Neutrons Neutrons are produced as

byproducts of various reactions and are therefore moderately significant as portions of human or environmental exposure

We can learn things from neutron studies that will help us in understanding the ways that ions and other heavy particles interact with tissue


Neutrons: Elastic Scatter

Important up to ~14 MeV range

average over angles:

Energy imparted to nucleus:


How to average cos2:

Addition formula for cosine:– cos(A+B) = cosAcosB - sinAsinB– For A=B=, cos(2) = cos2 - sin2– Furthermore cos2 + sin2 = 1 so– cos2 = cos2 - (1 - cos2) = 2cos2 - 1– Therefore cos2 = (1 + cos2) / 2

This gives us the tools we need to integrate cos2 over an interval.

In general <f(x)> over an interval (a,b) is


<cos2>, continued


Significance in Elastic Scatter

Recall we said that for any value of q, the energy transferred to the target nucleus, Et, isEt = En (4MaMn)cos2 / (Ma + Mn)2

So the average energy imparted to the target nucleus is

<Et> = {En (4MaMn) / (Ma + Mn)2} <cos2> We just spent three pages proving <cos2>=1/2 Thus <Et> = 2EnMaMn / (Ma + Mn)2


Inelastic Scatter

Increasingly important at higher neutron energies


Neutrons: Other Mechanisms

(III) Nonelastic (75 MeV)

12C + n 9Be + KE ~1.75 MeV

(IV) Neutron Capture14N + n 14C + p1H + n 2H + 2.2 MeV

(V) Spallation: Nucleus fragments!

Need very high-energy neutrons ( > 100 MeV)


Free Radicals:Definitions and Illustrations

A free radical is defined as a molecular species containing an unpaired electron. It may be charged or uncharged.

Most biological free radicals, with the significant exception of superoxide (O2

- •), are uncharged.– OH- Hydroxide ion (9 protons, 10 electrons)– OH• Hydroxyl radical (9 protons, 9 electrons)

Moses Gomberg: Characterized the triphenylmethyl radical in 1900


Reactivity of free radicals Free radicals are reactive because the unpaired electrons

tend to seek out targets, either other unpaired electrons:H• + •H H2

… or other acceptors of unpaired electrons. Reactivities vary considerably depending on presence or

absence of stabilizing influences, such as channels through which the unpaired electron can be delocalized

In the absence of those channels, free radicals tend to recombine in picoseconds

With those channels, they can last seconds or longer, even at room temperature


Radical Stability

This has nothing to do with political psychology :-) Highly unstable free radicals tend not to stay around

long enough for ordinary spectroscopic methods to detect.

Radicals where the unpaired electron can be highly delocalized last long enough to detect.

Triphenylmethyl radical:

CH •C + H•


Cartoons of Electron Distributions in ions, molecules, and radicals

Hydroxyl radical(8 paired e-, 1 unpaired e-, 9 p+)

Hydroxide ion(10 paired e-, 9 p+)

Molecular oxygen(16 paired e-, 16 p+)

Superoxide ionic radical(16 paired e-, 1 unpaired e-, 16 p+)

O H:

:: •

H:

::O

:

O:

: : O:

::

O:

: : O:

::

•


10-16 - 10-12 s Scale Events and After

e-fast + H2O H2O+• + e- + e-

fast

e-fast + H2O e-

fast + H2O* H• + OH•

H+ + OH•

(<100 eV)

H2O H2O-•nH2O e-

aqSolvatedaqueoushydrated

(10-4s)

H+

AcidH• H2

~10-11s

H2OH•, OH•, e-

aq

O• O2

O2-•, H2O2

Ionization:

Activation:


Radiation Chemistry of Water Since biological tissue is mostly water, we’re very

interested in the products produced when water absorbs ionizing radiation

The reactive species formed out of water are responsible for a large fraction of the biological activities of radiation

Ordinary ions (H+, OH-, H3O+) are among these species, as is hydrogen peroxide (H2O2);

So are free radicals: H•, OH•, O2-•, HO2•

We often discuss the “solvated electron”, eaq-.


Fricke Dosimeter Bookkeeping tool for aqueous radical chemistry,

based on Fe2+ Fe3++ e-

ferrous ferric Sequence of reactions:

H• + O2 HO2• (i.e. H-O=O•)HO2• + Fe2+ HO2

- + Fe3+ HO2

- + H+ H2O2

OH• + Fe2+ Fe3+ + OH-

H2O2 + Fe2+ Fe3+ + OH- + OH• In absence of O2: H• + H2O OH• + H2


Fricke Dosimeter: bookkeeping

Each hydrogen radical H• causes the oxidation of three molecules of ferrous ion

H2O2 produced by radiolysis will oxidize two ferrous ions: one directly, one indirectly.

A radiolytically-produced OH• radical gives rise to one more oxidation

Therefore at acidic pH in the presence of oxygen,G(Fe3+) = 2G(H2O2) + 3G(H•) + G(OH•)


Definition of Yield

G = Yield Number of events produced per 100 eV energy deposition

We’re often interested in dG(E)/dE

Yield is either dimensionless or has dimensions of (energy)-1 depending on your perspective

Fricke dosimeter provides a way of measuring yield


Fricke bookkeeping Results on p. 112 for 60Co photons:

G(H•) = 3.65G(H2O2) = 0.75G(OH•) = 3.15

We then apply formula 6.8 to determine G(Fe3+) Recall that under appropriate conditions

G(Fe3+) = 3 * G(H•) + 2 * G(H2O2) + G(OH•)= 3 * 3.65 + 2* 0.75 + 3.15 = 15.6

Under anaerobic conditions: eqn. 6.9 applies: G(Fe3+) = G(H•) + G(OH•) + 2G(H2O2) = 8.3


Interactions of Energetic Electrons With Biological Tissue

Direct

e-fast + DNA DNAbroken+e-

fast

e-fast + Protein Proteinbroken+e-

fast

Indirect Action

H2O* + e-fast

e-fast + H2O

H2O+• + e-H2O+e-

fast

log - lineardose - response

biol response

furtherradicalchemistry


Direct Action: the model

Direct action of radiation on a species says that a single hit of radiation onto a molecule damages it. Then if N is the number of undamaged molecules after irradiation with dose D, we expect the change in N, N, with a small increase D in dose is proportional to N and to D.

* * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * * * * * *

N0 Total moleculesN Undamaged molecules

Radiation in


Physical model and mathematics

Let N = number of undamaged molecules after irradiation with dose D. Then dN N dD.

More radiation dose implies more response More undamaged molecules implies more

damage.

A A+ + e-

or other chemistry


Why should the damage be log-linear?

The relationship dN N dD can be rewritten dN = -kN dD, where k = inactivation constant.

Then dN / N = -kdD. Integrating both sides, ln N = -kD + C. Raising e to a power on both sides, elnN = e(-kD+ C) = e-kD * eC. Defining eC = N0,

N = N0e-kD

Thus the physical meaning (boundary condition) of N0

is that it is the number of entities present in the case where the dose is 0.


Significance of the inactivation constant

Inactivation constant, k, is in dimensions of inverse dose (e.g. units of Gy-1) and is the reciprocal of the dose required to reduce the number of undamaged molecules down to 1/e times the original count.

N = N0e-kD; if Di = 1/k, then N(Di)= N0e-kDi = N0e-k/k = N0e-1 = N0/e We could define a half-inactivation dose D1/2, analogous to the half-life of an emitter:

For D =D1/2, N=N0/2 = N0e-kD1/2, ln1/2 = -kD1/2

Thus -ln2 = -kD1/2,so D1/2 = (ln 2)/ k = 0.693 / k


Indirect action of radiation

Initial absorption of radiative energy gives rise to secondary chemical events

Specifically, in biological tissue R + H2O H2O* (R = radiation)

H2O* + biological macromolecules damaged biological macromolecules

The species “H2O*” may be a free radical or an ion, but it’s certainly an activated species derived from water.

Effects are usually temperature-dependent, because they depend on diffusion of the reactive species to the biological macromolecule.


Dose-response for indirect action

Unlike the direct-action case, we can’t write down a simple mathematical model for what’s going to happen. The dose-response curve may be log-linear, but it doesn’t have to be:

ln(S

urvi

ving

Fra

ctio

n)

Dose


Interaction of energetic electrons with biological tissue

Direct action:e-fast + DNA DNAbroken + e-fast (log-linear)e-fast + protein proteinbroken + e-fast (log-linear)dN/dD = -k*D; Nundamaged = N0e-kD

Indirect action:H2O* + e-

fast

e-fast + H2O further radical

chemistry H2O+. + e-

H2O + e-fast

(water molecules) + (biomolecules) (biomolecules)* + radical water products


Radical Fates/Damaged Biomolecule Fates

Recombination A• + B• A - B (timescale 10-11s)

Generally A = B i.e. A• + •A A - A Restitution: Non catalyzed regeneration of non-radical

species (microsecond timescale)

A• + X A + X•

Repair: Catalyzed regeneration of undamaged species

A• + E + R Amod + E + R• where E is enzyme (ms-sec)

biolmolecule

diffuseablebiol

out

biolbiol

Fundamentals of Biology for the Radiation Biophysicist

It would be presumptuous of me to try to summarize all of biology in half of one lecture

I’ll therefore content myself with pointing out a few fundamentals that will be relevant to our studies of the interactions between ionizing radiation and biological tissue

As an endpoint, we’re primarily concerned with the effects of radiation on vertebrate, especially human, tissues; but we do need to have some feel for how radiation affects bacteria and yeast as well


What is life?

That was the title of a series of lectures given by Erwin Schrödinger in Dublin in 1943

His focus was on articulating how quantum physics could help to explain the organizational principles found in organisms

But we can kidnap that name to focus on what we actually do want to do, which is differentiate living organisms from non-living entities


What are living organisms?

Entities capable of:– Reproduction– Energy processing– Adaptation to changes in environment– Capable of local decreases in entropy


Based on that definition,what is alive?

On this basis, conventional life from archaea and eubacteria up through elephants and redwood trees are living

Viruses are a borderline case; prions highly questionable


Organisms are made up of cells

Cells are somewhat self-contained objects within which chemical reactions and reproduction can occur

Every cell interacts with its environment Cells are surrounded by a differentially

permeable boundary called a cell membrane Sizes of cells vary but they’re generally between

1 and 10 micrometers on a side


Highest-level taxonomic distinctions

Most fundamental distinction is made on the basis of whether the organism’s cells have nuclei

– Eukaryotic cells have nuclei– Prokaryotic (archaeal and eubacterial)

cells don’t Eubacteria are simple, generally

unicellular, organisms lacking nuclei Archaea are like that too, but they appear

to derive from a separate evolutionary history; many are extremophiles


Eukaryotes

These organisms have nuclei and generally have other definable organelles as well: mitochondria, endoplasmic reticulum, Golgi apparatus, vacuoles, chloroplasts, …

Often but not always multicellular Yeast, e.g. Saccharomyces, is a

unicellular eukaryote Some organisms are complex but

unicellular


Reproduction

We included this in our definition of life Unicellular organisms generally reproduce by fission,

but not inevitably; there are cooperative (sexual) events that occur even among bacteria

Multicellular organisms undergo mitosis at the cellular level but they also have a level of organization wherein an entire organism can be engendered via combinations of meiosis, mitosis, and growth


Eukaryotic organelles

Nucleus: site of replication and transcriptioncontains DNA in various levels of organization

Mitochondrion: site of most catabolic (energy-producing) reactions, which typically yield ATP

Endoplasmic reticulum: vehicle for lipid synthesis and protein processing

Golgi apparatus: vehicle for trafficking Cytoskeleton: stiff proteinaceous organizers Vacuoles: sacs containing fluids Chloroplasts: sites of photosynthesis


How do we study biological systems?

Observations of ecosystems Direct observations of whole organisms Recognition of tissue-tissue interactions Delineation of tissue types Recognition of cell-cell interactions Delineation of cell types Characterization of molecular events in a cell

and in the extracellular matrix Understanding of the underlying physics that

enables those molecular events to occur


Biological activity depends on chemistry

That’s a commonplace now, but it wasn’t fully recognized until sometime in the nineteenth century

It applies to chemical transformations within cells, but it also applies to extracellular systems and macroscopic movements, such as muscle contraction

Understanding the energetics (does the activity require or release energy) and the kinetics (how does one overcome an activation barrier) is critical to understanding biochemical processes


Biological reactions are catalyzed

A catalyst is an entity that participates in a reaction but is ultimately returned to its original state after the reaction completes

Therefore a catalyst influences kinetics but not equilibrium

Biological catalysts are called enzymes Enzymes have three fundamental properties:

– They are catalytic– They are specific– They can be regulated


Most, but not all, enzymes are proteins

Note that many proteins aren’t enzymes The recognition that enzymes are proteins arose in

the 1920’s and 1930’s By the 1970’s it became clear that certain RNA

molecules are catalytic Some RNA-catalyzed reactions, notably the creation

of new protein molecules, are central to biological function


DNA is the vehicle for heritance

Deoxyribonucleic acid is a polymer found in all organisms and many viruses

Building blocks: phosphodeoxyribose backbone,N-containing side-groups called nucleic acid bases

DNA contains information enabling parent cell or organism to produce nearly-identical offspring

Differences arise from:– Mutations– Recombination– Sexual segregation of chromosomes– Epigenetic effects


Central dogma, modern form

DNA becomes replicated prior to each cell division– Double-stranded DNA uncoils– Fresh copy of each strand created and coiled up

DNA is transcribed into various forms of RNA– Gene transcribed when RNA is called for– One strand of DNA provides template

Messenger RNA is translated at ribosome:– mRNA sequence defines amino acid sequence of

resulting protein– Protein then folds, either spontaneously or not


DNA replication is protected against error

Inherent error rate might be one base substitution in 104 or 105 replicated bases

Error correction within DNA polymerase drops that to about 1 in 107

Further error correction (“repair”) by external enzymes drops it to about 1 in 109


Why is that relevant?

In the human genome, 1 in 109 is still several surviving base substitutions in each replication!

Most substitutions are harmful; most aren’t fatal Exposure to ionizing radiation and certain

chemical mutagens, particularly at certain stages in the cell cycle, can significantly increase the error rate

Human genetic conditions that hinder DNA repair substantially increase radiation sensitivity


6/10/14 Rad Bio: interactions with matter p. 1 of 85 Illinois Institute of Technology PHYS 561...

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Transcript of 6/10/14 Rad Bio: interactions with matter p. 1 of 85 Illinois Institute of Technology PHYS 561...