Lecture content

9)

Entropic forces

1)

Introduction

2)

Thermodynamics

3)

Inter- and intra-molecular interactions

5)

Transport processes

6)

Biological Membranes

7)

Bioenergetics

4)

Diffusion

10)

Selected biophysical methods

8)

Neuron

Suggested

reading

Biochemistry

(5th edition). Lubert Stryer.

Freeman, NY 2002.

Biochemistry

(3rd edition) Mathews, van Holde

and Ahern. Benjamin/Cummings, CA 1999.

Introduction to Protein Structure

(2nd Ed.)

Branden & Tooze. Garland, NY 1998.

The Chemistry of Life

Steven Rose. Penguin,

London 1999.

Physical Chemistry

(5th edition). P.W. Atkins.

Oxford University Press, 1994.

http://biosci.umn.edu/biophys/OLTB

Biofizyka - Podręcznik dla studentów

(2002)

pod red. F.Jaroszyka, Wydawnictwo PZWL

Biofizyka kwasów nukleinowych dla biologów

(2000) pod red. Marii Bryszewskiej i Wandy Leyko,
Wydawnictwo Naukowe PWN

What is Biophysics?



Force generation

: muscle,

cell motility



Cellular mechanics

:

membranes, DNA, proteins



Molecular dynamics

:

interactions that control gene
expression



Signal

propagation

:

neurons,

sensory

cells,

chemotaxis

Biophysics is

… the development and use of

instrumentation

to

study

biological

macromolecules and processes



Chromatograph

y



Probes/Sensor

s



Microscopy



Spectroscopy



Micro

manipulation/fluidics



Simulation/Informati

cs

Biophysics is

… the science in

which physical concepts are
used to explain biological
phenomena

12.04.21

Sequence:

Sequence of DNA and Proteins

Structure:

3D Structure of Proteins

and other biomolecules and
molecular complexes

Interactions:

How

molecules

interact?

The object ..........

aaaaklm
t

ala ma kota

Processes exists at many time

scales



hierarchies of processes



Macromolecules have a hierarchy of structures.



Molecular machines have a hierarchy of states.



Biological processes have a hierarchy of pathways.

Length scale

Energy

Conformational changes1-10 kT

Protein Folding

6 - 30 kT

Biotin-Avidin
bond

35 kT

The surface of the channel
defines the volume that is
accessible to a probe of
radius 0.14 nm, about the
size of a water molecule.

Biology works with kT

Stochasticity is a major constraint

1kT = 0.62 kcal/mole (at

T=300K)

kT

G

e

y

Probabilit







Molecular Forces

A water molecule has one billion thermal collisions
with other molecules every second.

How

long

before

a

covalent

bond

is

broken?

e

-100

~10

-44

10

-44

10

9

/sec = 10

-

35

/sec

10

7

sec = 1 year

~ 10

28

years!

For covalent bonds G ~

100 kT

How long before a
hydrogen bond is broken?

For hydrogen bonds G ~ 1.3 kT

e

-1.3

~ 0.3

0.3 10

9

times/sec

A few nanoseconds!

All have

low atomic numbers

& are easily

reactive &

form

covalent bond

99%

of LIVING MATTER is made of

C, H, O, N, P, S

Molecular Composition of Cells

Molecule

% of Total Cell Weight

Small Molecules

(74% of Total

Cell Weight)

ions and other inorganics

1.2

sugars

1

fatty acids

1

individual amino acids

0.4

individual nucleotides

0.4

water

70

Medium & Big Molecules

(26% of Total

Cell Weight)

protein

15

RNA

6

DNA

1

lipids

2

polysaccharides

2

Covalent

bonds

Bond

Energy

Kcal/mol

Single covalent
bonds

O – H

110

H – H

104

C – H

99

C – O

84

C – C

83

S – H

81

C – N

70

C – S

62

Double bonds

C = O

170

C = N

147

C = C

146

Life is based on simple
non-living building block
molecules.

Selected numbers

3000M

>97M

.58M

Bases

25

7

1

DNAs

34k-150k

>19k

.48k

Genes

.2-3M

>30k

.4k

RNAs

.3-10M

>50k

.6k

Proteins

10

14

959

1

Cells

Human

Worm

Mycoplasma

Conformation

- surface

outline

or

contour

or

3-D

orientation

of chemical groups that are free to assume

different positions in space without breaking any bonds
thanks to:



free rotation

of atoms about a single chemical bond



non-covalent forces

hold atoms in spatial arrays

The folding of

a

mcacromolecu

le

Protein

1000 amino acid residues, 20 amino acids

need

ln20/ln2 = 4.32  

 bits to code each residue

I

total

= 4 bits 1000 residues = 4000 bits

average mass of amino acid residue = 118.9 amu

average information = 4.32/118.9 =

36.310



bits amu

-1

Protein and DNA information carring capacity

How many bits of information are required to code a 1000 unit
strand of DNA using 4 base units (CATG), and a protein using 20
possible amino acids? How efficient is the storage in terms of
mass of the respective molecules?

DNA

1000 base pairs, 4 units (CATG) have ln4/ln2 = 2bits to

code each pair

I

total

= 2 bits 1000 base pairs = 2000 bits

average mass of (CATG) = 307.5 amu

average information = 2/(2 

 

 





  



bits amu

-1

There are 10 times more information

per mass unit in protein than DNA!

For centuries, life was defined

in the unit of the whole

organism...a cat, a bird, a

human being.

Unlike atoms and simple

molecules studied in

chemistry and physics, no

two cells are identical

.

Life is

manifested in

the CELL

The Definition of Life rests

in the

Definition of a Cell

...

... self contained

... self assembling

... self adjusting

... self perpetuating

... isothermal mix of biomolecules,

... held in a 3-D conformation by weak non-covalent forces,

... can extract raw materials & free energy from its
surroundings,

... can catalyze reactions with specific
biocatalysts (enzymes), which it makes itself,
... shows great efficiency & economy of
metabolic regulation,

... can self-replicate, using the linear information, in
the "molecule of life"…

DNA

.

... maintains a dynamic steady state far from equilibrium,

Eukaryote

E. Coli

Crowding !!!!

Biochemical

reactions in living

systems take place in

media containing 50–

400 mg/ml of

macromolecules.

Experimentally observed crowding and

confinement effects on macromolecular

reactions

Observation

Magnitude



Enhancement

of

spectrin

self-

association by PEG,
dextran.

10-fold

increase

of

association

constant

in 20% dextran.



Enhancement of actin

polymerization

by

dextran and PEG

3-fold decrease in
solubility

in

15%

dextran



Stabilization of supercoiled conformations of DNA by PEG



Enhancement

of

large

linear

DNA

condensation by PEG.

> 10-fold increase in 2-
state

equilibrium

constant at 18% PEG

Biological Design

There is a

recurring patterns of

spirals

,

triangulated

forms

,

&

pentagons

in everything from

crystals

to

proteins

,

viruses

to

plankton

.

TENSEGRITY is a fundamental aspect of

SELF-ASSEMBLY -

an architectural

system, mechanically stable, yet

dynamic, where the forces of tension and

compression balance.

Tensegrity may be the

most

economical

and

efficient

way to build

cell structure.

Living systems are far from equilibrium

.

A numerical measure of how far a
reaction is from equilibrium

S

T

H

G











The law of entropy can be

temporarily blocked (Life), but it

can never be violated.

It is maintained by the
action

of

complex

regulatory systems.

Networks

of

interconnecting

partially redundant systems that
use

antagonistic interplay

making

them stable to internal-external
changes.

Homeostasis

Coupling reactions that are energetically

unfavorable with reactions that are

energetically favored done by linking

hydrolysis

of ATP

(favored) to reactions linking atoms

together (not favored), creating new biological

order.

Design of Metabolism

Anabolic reaction

- biosynthesis

Catabolic reaction -

oxidation (removal) of e-’s

from foodstuffs

1.

Digestion of polymers (foods) into monomers

2.

GLYCO-LYSIS

3.

Oxidation CO

2

+ NADH



H

2

O

ADP + P



ATP

4.

Phosphorylation

Biochemical
autonomy

Biochemical activities in cells
produces energy & molecules to
sustain cell functioning.

Metabolic reactions

– are violent events

inside cells, carefully controlled by

ENZYMES

Transmembrane ion gradients

Mitichindrium

Chloroplast

The release of stored

energy is coupled to

thermodynamically

unfavorable reactions.

1.

Various number of proteins per cell,

2.

Different salinity, temperature and pH,

3.

Nutrient level.

Robustness

– the important task of the cell can

be completed even as conditions vary.

Engineering Cells for
Robustness

Cells Have

Different

Compartmen

ts for

Different

Functions

Specialized Functions Require Phase
Change:

Many functions of cells are so complex that the phase
of the cell must be altered through changes in state of
many proteins or expression.

Cells undergo a rapid
switch from one phase
to another with the
appropriate signal.

Phase Changes Are Discontinuous:

Cells Have Different Phases for

Different Functions