Lecture1:

TheScopeandTopicsofBiophysics
Lecturer:
BrigitaUrbanc
Office:12909
(Email:brigita@drexel.edu)
Coursewebsite:
www.physics.drexel.edu/~brigita/COURSES/BIOPHYS_20112012/
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BIRTHOFBIOPHYSICS
Advancedinterdisciplinaryscienceinvolving:
physics,biology,chemistry,mathematics;
New,60100yearsolddiscipline:

1892:KarlPearson(missinglinkbetweenbiologyand
physics=>namebiophysics)
1943:ErwinSchrodinger(NobelPrize,1933)
lectureseries:WhatisLife
1946:BiophysicsResearchUnit,King'sCollege,
London,hirephysiciststoworkonquestions
ofbiologicalsignificance;MauriceWilkins,
RosalindFranklin:XraydiffractionofDNA
1953:FrancisCrick(particlephysicistturnedinto
biophysicistatCambridge)andJamesWatson
(biologist):doublehelixstructureofDNA
1957:TheBiophysicalSocietyfounded
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BIOPHYSICALTOPICS
Biophysicaltopicsbasedonrelativesizeofthesubject:
molecularandsubcellularbiophysics
physiologicalandanatomicalbiophysics
environmentalbiophysics

Biophysicaltechniquesandapplications:
generalbiophysicaltechniques
imagingbiophysics
medicalbiophysics

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MolecularandSubcellularBiophysics
TheStructureandConformationofBiologicalMolecules
StructureFunctionRelationships
ConformationalTransitions
LigandBindingandIntermolecularBinding
DiffusionandMolecularTransport
MembraneBiophysics
DNAandNucleicAcidBiophysics
ProteinBiophysics
EnergyFlowandBioenergetics
Thermodynamics
StatisticalMechanics
Kinetics
MolecularMachines
Allosterics
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BiophysicalTechniquesandApplications
Ultracentrifugationtoseparatemoleculesofdifferentsizesbasedonthe
sedimentationprinciple,upto106g;
Electrophoresistoseparatemoleculesofdifferentmolecularmass/size
basedonthesedimentationprinciple;electricfieldactsonthecharged
molecules;gelelectrophoresis
SizeExclusionChromatography(SEC)usestightlypackedgelbeadsand
sedimentationbasedongravity(andsometimespressure)totrapsmall
moleculesandallowlargermoleculestopassthroughthegelfasterthan
smallmolecules;
SpectroscopymostlywithincidentEMradiationandmeasuringthe
intensity/direction/polarizationoftheemittedradiation(originallyonly
thevisiblespectrum380750nmwasused;nowalsoUVandIR);in
additiontoEMalsoelectronandmassspectroscopy;
AbsorptionSpectroscopytofinde.g.theconcentrationofmoleculesinthe
solutionbyusingEMofaparticulartoshineonthesampleand
measuretheintensitythatcomesoutORabsorbanceversustoidentify
thetypeofmolecules;

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FluorescenceSpectroscopytocharacterizemoleculesandtofollow

conformationaltransitions;causedbyabsorptionataonewavelength
andemissionatalongerwavelength(electronsdropfromtheirexcited
energystateemittinglight;
MassSpectrometrytomeasuremassormolecularweightofmolecules;
moleculesareionizedinavacuum,thenpassedthroughamagneticfield;
XRayCrystallographytodeterminetherelativepositionsofatomswithin
acrystalbyusingdiffractionona3Dcrystallattice;highresolutionof
structuraldetailsbutthemoleculesneedtobeinacrystallinephase;
NuclearMagneticResonanceSpectroscopy(NMR)toobtainstructural
informationaboutmoleculesofthehighestresolutionusingEMofaradio
frequency,whichinteractswithnuclearspinsofatomsinalargemagnetic
field,causingthemtojumpbetweenthespinstatesandemitatdifferent
dependingonthelocalstructurearoundtheatom;
ElectronMicroscopytoviewobjects1,0002,500smallerthanthoseseenby
lightmicroscopes(electronsofasmallwavelengthareusedinsteadofEM);
transmissionEM(TEM)andscanningelectronmicroscopy(SEM);
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AtomicForceMicroscopy(AFM)withresolutionsimilartoTEM,3D

featureslikeSEM;amechanicalprobe(atip)movesalongthesurfaceof
thescannedobjecttoobtain3Dinformation;
OpticalTweezerstoholdandmanipulatemicroscopicparticlesevensingle
moleculesoratomsusingfocusedlaserbeamstocreateforcesoftheorder
ofpN=1012N(0.1nmto10,000nmsizeobjects)andmeasureforces
neededtobendorbreakDNA,forexample;
VoltageClampisusedinelectrophysiologytodetermineelectriccurrents
incells,inparticularneurons;afinemicroelectrodeisinsertedintothecell
withanotherincontactwiththesurroundingfluidwhilethevoltageis
clamped(heldconstant)byafeedbackthatgeneratesacountercurrentto
thatgeneratedbythecell;
CurrentClampisanalogoustovoltageclamp;thecurrentisclamped(held
constant)andthevoltagechangeinducedbythecellmeasured;
PatchClampisalternativetovoltage/currentclamp;theelectrodeisplaced
insideamicropipettewithelectrolytesolutionandthemicropipette
combinedwithagentlesuctionelectricallyisolatesasmallpatchonthe
membrane;enablestostudyasingleionchannelwithinthemembrane;
CalorimetrymeasuresC orC versusT:transitionsorligandbinding.
P
V
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FourClassesof
Macromolecules:
(A)DNAinaBform
(B)Protein(hemoglobin)
(C)Lipidmolecule
(phosphatidylcholine)
(D)Branchedcomplex
carbohydrate

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PolymerNatureof
Macromolecules:
(1)DNAandRNA
molecules:made
ofnucleicacids
(2)proteins:made
ofaminoacids

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DNAcartoonanddetailedchemicalstructure

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EachDNA
moleculeis
polymersoffour
nucleicacids:
A,T,G,C

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Nucleicacidswithin
adoublestrandDNA:
Backbonegroups:
deoxyribose
phosphate

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mRNAencodes
Proteins:
nucleotideto
aminoacid
sequences

Uracil
(insteadof
Thymine)

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20natural
aminoacids
hydrophobic
(hatewater)

hydrophilic
(lovewater)

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Mostcommonchemicalgroupsfoundinproteins:

CHNOPSacronym:elementsmostcommonlyfoundincells
(accountsforabout98%ofallatoms)
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TwoAminoacidsFormaPeptideBond

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Membraneisalipidbilayer.
lipidmolecule

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StructureofaCell
plants,animals(mostlymulticelullar;alsoamoeba)

bacteria,archaea(unicellularorganisms)
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MajorCellCompartments
nucleus:approximatelysphericalmembraneboundorganellenearthecenterof
acell;containsalmostallofcell'sgenome;functions:geneexpression
(transcriptionofDNAtoRNAtomakeproteins),DNAreplicationpriortocell
division;surroundedbyadoublemembranecallednuclearenvelope(membrane);
theoutermembraneconnectedtoroughER;
endoplasmicreticulum(ER):isanetworkoffoldedmembraneswithlargesurface
tofacilitateprocesses;roughERhostsribosomes,wherethesynthesisofproteins
occurs;smoothERcontainslipidvesiclesandisinvolvedinlipidandsteroid
synthesis;ERalsoinvolvedinaddingcarbohydratestoproteins,splicingand
foldingpeptides,andpackagingproteinsintolipidvesiclesfortransporttoother
partsofthecell;
Golgiapparatus:similartosmoothER(foldedmembrane);functions:processing
andpackagingoflipidsandproteins,breakdownofcarbohydratesandlipids;
vesicles:smallsphericalbilayercontainers,theyfusewithorbudfromthe
plasmamembrane;lysosomes:vesicleswithenzymeslysozymestobreakdownor
digestlargermolecules;peroxisomes:vesiclesthatbreakdownlongchainfatty
acids;

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vacuoles:giantvesicleswithoutaparticularshape;functions:isolateharmful
objectsandwasteproducts,helpmaintaincorrecthydrostaticpressure;
ribosomes:largecomplexofproteins,enzymes,andribosomalRNA(rRNA)
foundinbothprokaryotesandeukaryotes;function:proteinsynthesisaccording
tothesequenceofmessengerRNA(mRNA);
mitohondria:membraneboundorganelles,alsocontainDNA(mtDNA);function:
ATP(adeninetriphosphate)synthesis,convertenergystoredinfoodintohigh
energyphosphatebondsofATP;
chloroplasts:organellesmostlyfoundinplantcells(greenparts),carryout
photosynthesis(capturelightandconvertitintochemicalbondenergyof
carbohydratesandATP);
cytoskeleton:interconnectedtubeorropelikefibrousstructuresmadeof
proteins;function:tosupport,transmit,orapplyforces,topreservetheshapeof
thecellandanchorvariousorganellesinplace;threetypes:microtubules,
intermediatefilaments,andmicrofilaments;
DNA:mostsignificantstructureinsidethecellwithgeneticmaterialorganizedin
chromosomes:eachchromosomeisasingleDNAmolecule;sometimesDNAis
organizedintocomplexeswithproteins;allchromosomesinacell=cell'sgenome.

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LifeCycleofanEukaryoticCell

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Whatisthegoalofbiophysics?
(1)Createsimplifiedmodelsofbiologicalsystems
(2)Makequantitativepredictions
(3)Experimentallytestquantitativepredictions

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DNAmodels:

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Proteinmodels:

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Membranemodels:

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