IX. Fundamental Principles of Nanobiotechnology

1
IX. Fundamental Principles of Nanobiotechnology
2
An Eaxample MicroRNA for Disease Control
3
Natural organization of life

• Eukaryotic cells
• Internal membranes surrounding
• DNA (nucleus)
• Electron transport machinery (mitochondria)
• Photosynthetic appartus (chloroplasts)
• Plant cells have a thick outer wall
• Prokaryotic cells
• No membrane-enclosed internal structures
• Cell walls made of sugars and proteins
• Evolutionarily distinct though functionally
  analogous molecular machinery makes them
  susceptible to different kinds of drugs

HIV virus
bacteriophage T4

• Viruses
• Cannot reproduce outside a host cell
• Not actually alive
• Eukaryotic viruses may be enclosed in protein or
  lipid coatsMay contain DNA or RNA
• Prokaryotic viruses are called bacteriophage
• Typically DNA enclosed in a protein coat

4
Scales of life
Nucleus Smallpox viruses inside a eukaryotic
cell
Bacterial viruses on the surface of a bacterial
cell
5
Intracellular environmentRedox state
Effective E (mV)
Human respiratory tract fluids 200
Human white blood cell cytoplasm 50
Human nerve cell cytoplasm 20
Human red blood cell cytoplasm -200
Human brain cell cytoplasm -215
Rat bile -180
Rat liver cell cytoplasm -205
Rat liver cell mitochondria -260
The intracellular concentrations of redox-active
molecules and the ratios of their oxidized and
reduced forms poise the effective reductive
capacity of the intracellular fluids. The more
negative the value of the effective reduction
potential (Eeff) the larger the reductive
capability of those fluids.
Adapted from Martinovich, et al. Eur. Biophys. J.
34937-42. 2005.
6
Intracellular environmentWater availability and
solute concentrations
Water contents red blood cells (64), frog heart
cells (80), frog egg (49)
Intracellular solutions contain more K ions
Ion Ionic radius Surface charge density Molar ionic volume Intra-cellular Extra-cellular Water preference
Ca2 100 pm 2.11 -28.9 cm3 0.1 µM 2.5 mM High density
Na 102 pm 1.00 -6.7 cm3 10 mM 150 mM High density
K 138 pm 0.56 3.5 cm3 159 mM 4 mM Low density

• The interactions between water and Na are
  stronger than those between water molecules,
  which in turn are stronger than those between
  water and K ions.
• The distance between the Na ions and water is
  shorter than between two water molecules which is
  shorter than between K ions and water.
• Ca2 ions have stronger destructive effects on
  the hydrogen bonding than Na ions.

From www.lsbu.ac.uk/water/cell.html
7
Intracellular environmentTemperature limits of
life
8
Cross section of a portion of an Escherichia coli
bacterial cell
Intracellular environmentMacromolecular
interactions
The cell wall, with two concentric membranes
studded with transmembrane proteins, is shown in
green. A large flagellar motor crosses the entire
wall, turning the flagellum that extends upwards
from the surface. The cytoplasmic area is colored
blue and purple. The large purple molecules are
ribosomes and the small, L-shaped maroon
molecules are tRNA, and the white strands are
mRNA. Enzymes are shown in blue. The nucleoid
region is shown in yellow and orange, with the
long DNA circle shown in yellow, wrapped around
HU protein (bacterial nucleosomes). In the center
of the nucleoid region shown here, you might find
a replication fork, with DNA polymerase (in
red-orange) replicating new DNA.
Illustration and text by David Goodsell,
http//mgl.scripps.edu/people/goodsell/illustratio
n/public