Lecture 2' - Cellular Environments

8/14/2019 Lecture 2' - Cellular Environments

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Lecture 2 CellularEnvironments


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The Cellular Environment

Environment plays a large role in determiningmacromolecular structure.

The strength of long range interactions: Is inversely proportional to the dielectric constant, .

Also: potential for direct interaction with solventmolecules.

There are number of distinct cellularenvironments

These are divisible into two categories: Aqueous (Aq) Environment:

dominant, since the cell is ~ 70% H20.

Also many Non-aqueous Environments: interior of membranes; interfaces between folded structures; interior of folded proteins.


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The Structure of Water

First, we consider the Aqueous (Aq)environment:

the dominant cellular environment. our focus: an understanding of water structure.

Water exhibits structure at several levels: Individual H20 molecule:

particular interest: gross electronic structure.

Structures adopted by interacting H20 molecules:

ice well-characterized crystalline structure;

liquid water also generally well-organized.

Water structure has profound implications forthe behavior of dissolved substances.

including biological macromolecules.


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The H20 Molecule

In liquid water, H20 is roughly tetrahedral

(pyramid-like) central, sp3-hybridized Oxygen.

two sp3

orbitals bonded to Hydrogen atoms. angle b/w O-H bonds: ~104.5o.

two sp3 orbitals hold non-bonding e- pairs. slightly greater repulsion than O-H bonds.

Note: In a H-bonded network, all 4 nearly identical.


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H20 is a Polar Molecule

H20 contains 4 permanent

dipoles Generally, a dipole is formed by charge

separation:

two small, opposite charges of the samestrength

- to + , are separated by a distance, d.

Dipoles like to interact with charges, eachother

Water has one dipole per pyramidapex: Each O-H bond is polarized, since O is

much more electronegative than H.

e- are localized around the Oxygen.

Result: permanent dipole moment, directed from - to + O to H .


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H20 is also Highly Polarizable

The strength, || of each of H20s dipolemoments is highly variable. || tends to increase around charges, or other

dipoles:

Isolated H20 molecule: || = q*d = 1.855 debye.

In a cluster of 6 or more: || = 2.6 debye.

In Ice: || = 3.0 debye.

this tendency to change, based on environment

is referred to as polarizability.

H20 is thus both polar and highly

polarizable:

very high dielectric constant (

80).

I / 2 H 0


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Interact on /w 2 H20

Molecules

Dominated by an interaction between dipoles: The dipole moment of the O-H bond of the first H20;

The dipole moment of the non-bonding e- pair of the2nd H20.

This dipole-dipole interaction: aligns these two dipoles head-to-tail, to be co-linear.

brings the associated O and H atoms closer than thesum of their Van der Waals radii forming the water-water Hydrogen Bond (H-bond). O-H is the H-bond donor.

non-bonding e-

pair of the Oxygen is the H-bond acceptor.


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H-Bonded Pairs inBiopolymers

There are many types of H-bonds Several contribute greatly to the structure of

biopolymers.

Same basic character: the 2 dipoles are co-linear. nearly the same strength

Note: relative strengths determined

by bond-length

shorter is stronger.

Note that in Aq. solution: Intra-molecular H-bonds must

compete with H20.


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Water can form a H-bondedNetwork

Each H20 can participate in 4 H-bonds: twice as a donor (2 O-H bonds).

twice as an acceptor (2 unbonded e- pairs).

Normal, frozen water (0oC, 1 Atm pressure): forms a hexagonal H-bonded lattice.

Oxygens fixedbut, the protons (Hydrogens) ratherdisordered.

This form of ice is Ice I.


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Other Forms of Ice

Removing the proton disorder requires work: lower T; much higher pressure (P > 20 kbars

20,000 atm). the resulting hexagonal lattice is Ice VIII.

Various other forms of ice also exist note Ice IX forms a pentagonal structure.


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The Structure of Liquid Water

Structure of pure liquid water quite similar toIce I. also an H-bonded network.

H20 moleculeswell-organized at the air-water

interface highly cohesive network.

A similar interface forms at the surface of dissolvedmolecules.

However, structure much more dynamic thanice. the pattern of H-bonding changes about every

picosecond.

results in a net dissociation of H20 into [H30+] and

[OH-

]:


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Interaction of DissolvedMolecules with Water

When a molecule is placed in water: a water envelope forms around the molecule,

whether it is polar or not.

envelope is very similar to the air-water interface.

well-organized structure (Senvo < 0).

Formation thus unfavorable:

Genvo = -TSenv

o > 0.

Around ions, the envelope forms a

cage-like, clathrate structure: regular hexagonal and pentagonal

faces (see right).

The solubility of a dissolved molecule

depends on its ability to overcome this entropicpenalty


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Hydrophilic Compounds

For water-soluble compounds: the net interaction with water molecules(Gint

o) overcomes the negative Senv

o of forming the H20envelope:

Gneto

= Genvo

+

Ginto

< 0. termed hydrophilic(from the Greek philos =

love).

Note: Waters around hydrophilic substances typically form arrays of 6 and 7 H20s.

Examples: Salts interact by dissociating into pairs of charged

ions. e.g.: NaCl Na

+ + Cl-. interaction b/w water and the charged ions highly

favorable. ions are thus highly water-soluble.


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Hydrophobic Compounds

Substances that are neither charged nor polarin solution: do not interact appreciably with H20, and thus

cannot overcome the entropic penalty of the water

envelope. Are pushed out of solution (insoluble); Waters form rigid ice-like cages, with pentagonal

faces very low in entropy (similar to Ice IX).

Termed hydrophobic (from the Greek,phobos =fear).

e.g., Hydrocarbons, such as methane.

In contrast, Hydrophobic compounds quitesoluble in organic solvents (e.g., chloroform).

due to van der Waals interaction (with solvent). while hydrophilic compounds prefer to aggregate


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Amphipathic Molecules

Some molecules are hydrophobicand hydrophilic. referred to as amphipathic. e.g., a phospholipid molecule:

Head: phosphatidyl Choline(hydrophilic); Two charged groups: PO4

- + N(CH3)3+

Tail: long hydrocarbon chains(hydrophobic).

In water, these formaggregates so that each region may interact

with other groups of its own type: hydrophilic head: groups with H20.

hydrophobic tails: interact with air

or


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Structures Formed byAmphipathic Molecules

Several types of structures may form,depending on: type of amphipathic molecules;

concentration, temperature, etc.Typical structures:

Lipid monolayer: forms at air-water interface.

Globular micelles:

dilute phospholipid dispersions. internal hydrophobic environment.

Bilayer vesicles: define 2 hydrophilic environments. separated by 1 hydrophobic environment.

useful for establishing cell, organelle boundaries.


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Biopolymers also Amphipathic

Proteins: a mixture of polar and nonpolar amino acid residues. fold into structures resembling micelles:

basically globular.

hydrophilic residues displayed on the surface. hydrophobic residues buried in the interior.

Nucleic Acids: nitrogenous bases (hydrophobic rings).

negatively charged sugar-phosphate backbone(hydrophilic).

Bases pair and fold into the nucleic acid interior. e.g., in B-DNA (two aggregated DNA chains).

This is the basic principle of the hydrophobiceffect


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Non-aqueous Environmentsof Biopolymers

Many biomolecules exist in non-aqueousenvironments: mostly, these are proteins found in lipid bilayers.

reside amongst the hydrophobic tails.

Such molecules display an inverted topology: hydrophobic groups: exposed on the surface; hydrophilic groups: sequestered in the center.

Example: Gramicidin left-handed, anti-parallel double

helix. polar groups line the center

mimic the polar, water solvent; allows ions to pass an otherwise

impermeable bilayer. ion channel (monovalent cations).

Membrane Impermeable to


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Membrane Impermeable toIons

Hydrocarbon tails are much less polar than H20. in the membrane lower by a factor of 40.

membrane 2 vs. w 80.

long-range interactions (b/w charges, dipoles) 40x

stronger.The Self-Energy of a singly-charged ion, q:

Es = q2/(8rs) ; rs = Stokes radius

again-dependent: ionic self-energy also 40x greater.

Relative probabilities of existing in and out of themembrane Given by a ratio of Gibbs factors

P(in)/P(out) exp[- Es(in)/RT]/exp[- Es(out)/RT]

e-54 3.5 x 10-24. Thus, membrane virtually impermeable to ions


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Diffusion in Membranes is2-Dimensional

In membranes, molecules must travel in 2dimensions. strong implications for chemistry, diffusion-controlled

kinetics.Concentrations within membranes must beredefined: moles/area (M/mm2) used, instead of moles/volume

(M/mm

3

). For instance, for a sphere a 2-fold radius increase

accompanied by: an 8-fold dilution in concentration, for molecules in the

volume.

since V = 4/3 r

3

but only a 4-fold dilution, for molecules constrained to the


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The Interior of GlobularProteins

Another important non-polar environment is theinterior of a globular protein. primarily amino acids with non-polar side chains.

highly non-polar (typically, 2.5).

Charged ions will tend to avoid suchenvironments, due to an increased self-energy.

energetically difficult to bury an ion within a protein.In addition, amino acid residues which carry acharge:

(+) Lysine, Arginine;

(-) Aspartic acid, Glutamic acid.

will tend to be uncharged, within the interior

K V l f B i d


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pKa Values of Buried

Residues

Tendency of charged amino acids to adopt theuncharged form in a protein interior: will be reflected by a pKa change for these side

chains.

lower pKas = an increased tendency to dissociate.

For positively charged (basic) side-chains: Arginine (Arg), Lysine (Lys).

pKa will be lowerincreased tendency for the extra

H+ to dissociate from the residue.

For negatively charged (acidic) side-chains: Glutamic acid (Glu), Aspartic acid (Asp).

pKa will be higherincreased tendency for the

residue to neutralize by gaining an H+

.


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Conclusion

In this Lecture, we have discussed: The various Cellular Environments:

The Aqueous environment and Water Structure, The impact of water structure on the solubility of dissolved

substances.

Non-Aqueous environments, Such as the interior of lipid aggregates and proteins.

and discussed the impact of differences in mediumpolarity/polarizability ().

In the next Lecture, we begin our discussion ofsymmetry: Various types of simple symmetry. Its use in simplifying the description of biopolymer

structure;

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Lecture 2' - Cellular Environments