Nanotech Pushes Out Medical, Energy Frontiers

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27 October 2005

Nanotech Pushes Out Medical, Energy Frontiers, Scientist Says
Best yet to come from convergence of biotechnology, nanotechnology


DESIGNING NOVEL MATERIALS AND MOLECULAR MACHINES

By Shuguang Zhang
Associate Director, Center for Biomedical Engineering, Massachusetts
Institute of Technology

About 10,000 years ago, humans began to domesticate plants and
animals. Now it's time to domesticate molecules.
--Susan Lindquist, Whitehead Institute for Biomedical Research,
Massachusetts Institute of Technology

Biotechnology, which is known primarily by its medical and
agricultural applications, is increasingly being focused on the
building of new biological materials and machines in an astonishing
diversity of structures, functions, and uses. The advent of
nanotechnology has accelerated this trend. Learning from nature,
which over billions of years has honed and fashioned molecular
architectural motifs to perform a myriad of specific tasks,
nanobiotechnologists are now designing completely new molecular
patterns -- bit by bit, from the bottom up -- to build novel
materials and sophisticated molecular machines. Over the next
generation, advances such as new materials to repair damaged tissues
and molecular machines to harness solar energy from the smallest
molecular amino acids and lipids will likely have an enormous impact
on our society and the world's economy.

Modern biotechnology has already produced a wide array of useful
products, such as humanized insulin and new vaccines. But what lies
ahead can be even more revolutionary. That is why governments small
and large, and industries local and global, are increasingly seeking
to attract biotechnology talent and investment. There is no doubt
that biotechnology, helped by the tools of nanotechnology, is
expanding at an accelerating rate, and that the best is yet to come.

Imitating Nature

Nature itself is the grandmaster when it comes to building
extraordinary materials and molecular machines atom by atom and
molecule by molecule. Shells, pearls, corals, bones, teeth, wood,
silk, horn, collagen, muscle fibers, and extra-cellular matrices are
just a few examples of natural materials. Multifunctional
macromolecular assemblies, such as hemoglobin, polymerases, and
membrane channels, are all essentially exquisitely designed
molecular machines.

Through billions of years of molecular selection and evolution,
nature has produced a basic set of molecular building blocks that
includes 20 amino acids, a few nucleotides -- the structural units
of nucleic acids such as ribonucleic acid (RNA) and deoxyribonucleic
acid (DNA) -- a dozen or so lipid molecules, and two dozen sugars.
From these seemingly simple building blocks, natural processes are
capable of fashioning an enormously diverse range of fabrication
units that can further self-organize into refined structures,
materials, and molecular machines that not only have high precision,
flexibility, and error-correction capacity, but also are self-
sustaining and evolving. For example, the photosynthesis systems in
some bacteria and all green plants take sunlight and convert it into
chemical energy. When there is less sunlight, as, for example, in
deep water, the photosystems must evolve to become more efficient to
collect the sunlight.

In the early 1990s, biotechnologists began to learn how to
manipulate natural building blocks with at least one relevant
dimension being between one nanometer (one billionth of a meter) and
100 nanometers to fabricate new molecular structures, thus ushering
science and technology into the age of designed molecular materials.
Much like clay and water can be combined to make bricks with
multiple uses that, in turn, can be used to build walls such as the
Great Wall of China, houses, or roads, basic natural building blocks
such as amino acids can be used to create structures such as
peptides and proteins that can be used for a variety of purposes.
For example, animals grow hair or wool to keep themselves warm,
shellfish grow shells to protect their tissue from harm, spiders
spin silk to capture insects, and our cells make a lot of collagens
to keep cells together to form tissues and organs.

If we shrink the construction units one billion times to the
nanoscale, we can construct molecular materials and machines from
prefabricated units in a way similar to that in which a house is
assembled from prefabricated parts.

Peptides formed from amino acids are molecular architectural units
that are proving very useful in the development of new
nanobiological materials. In water and in the body fluids, these
peptides form well-ordered nanofiber scaffolds useful for growing
three-dimensional (3-D) tissue and for regenerative medicine. For
example, scientists have fabricated artificial cartilage and bones
to replace damaged tissue using the biological scaffolds and cells.
Furthermore, scientists have also shown that the designer self-
assembling peptide nanofibers can stop bleeding instantly, a
characteristic useful in surgeries. New peptides are proving to be
remarkably useful in drug, protein, and gene deliveries, because
they can encapsulate some water-insoluble drugs and ferry them into
cells and other areas of the body. They also are essential to
fabricating bio-solar, energy-harvesting molecular machines that use
the photosystem from spinach and tree leaves.

Molecular Self-assembly

All biomolecules, including peptides and proteins, naturally
interact and self-organize to form well-defined structures with
specific functions. By observing the processes by which these
biological molecular structures are assembled in nature,
nanobiotechnologists have begun to exploit self-assembly as a
fabrication tool for building new nanobiostructures such as
nanotubes for metal casting, nanovesicles for drug encapsulations,
and nanofiber scaffolds for growing new tissues.

Molecular self-assembly involves mostly weak bonds -- as does human
handholding -- that can be joined and disjoined quickly. This is in
sharp contrast to the very strong bonds that join our arms to our
body. Individually, weak molecular forces are quite insignificant.
Collectively, weak interactions such as the hydrogen bond and the
ionic bond play an indispensable role in all biological structures
and their interactions. The water-mediated hydrogen bond, in which
numerous water molecules work as a bridge to connect two separate
parts, is especially important for biological systems, since all
biological materials interact with water. The bond, found in all
collagens, works to increase the moisture for an extended time.

As to molecular building blocks, the designed peptides resemble the
toy Lego bricks that have both pegs and holes arranged in a
precisely determined manner and can be assembled into well-formed
structures. Often referred to as "peptide Legos," these new
molecular bricks under certain environmental conditions
spontaneously assemble into well-formed nanostructures.

In water, peptide Lego molecules self-assemble to form well-ordered
nanofibers that further associate to form scaffolds. One such
nanofiber scaffolding material that has been commercially realized
is PuraMatrix, so called because of its purity as a
biotechnologically designed biological scaffold. Biomedical
researchers currently use it worldwide to study cancer and stem
cells, as well as to repair bone tissue.

Since these nanofiber scaffolds contain 5 to 200 nanometer pores and
have extremely high water content, they are of potential utility in
the preparation of 3-D cell and tissue growth and in regenerative
medicine. In addition, the small pore size of these scaffolds may
allow drugs to be released slowly so people do not have to take
their medicine several times a day but rather once over a longer
period. A slow-release nanoscaffold device can be implanted on the
skin with medicine supplies sufficient for months or years.

Creating More Building Blocks

Using nature's lipids as a guide, a new class of lipid-like peptide
detergents has been designed. These peptides have seven to eight
amino acids, giving them a length similar to naturally occurring
lipids, which make up cell walls 20,000 times thinner than the
diameter of a piece of human hair.

Simple lipid-like peptide detergents produce remarkably complex and
dynamic structures in the same way that the assembly of numerous
simple bricks can make many different and distinctive architectural
structures.

Some peptide detergents have been found to be excellent materials
for stabilizing notoriously hard-to-stabilize membrane proteins --
protein molecules attached to or associated with the membrane of a
cell -- thus opening a new avenue for overcoming one of the biggest
challenges in biology: obtaining clear pictures of the ubiquitous
and vital membrane proteins.

Numerous drugs exert their effect through membrane proteins. But how
these drugs interact with vital membrane proteins at the finest
molecular level remains largely unknown. The designed peptide
detergents promise to change this. If we can fully understand the
interactions of these proteins, we may be able to produce more
effective and efficient drugs with few or no side effects.

Harnessing Solar Energy

Detailed molecular study of how membrane proteins function is just
an exercise in understanding them. By deepening our knowledge of how
cells communicate with their surroundings, we learn how all living
systems respond to their environments. With this know-how, modern
nanobiologists have begun to fabricate advanced molecular machines
able to develop extremely sensitive sensors for medical detection or
to harness bio-solar energy. For example, ancient Chinese doctors
smelled a patient to diagnose a medical problem because they
believed that an illness can change a patient's body odor or
secretion. In modern medical science, a number of instruments are
used to make an accurate diagnosis. In the future, a smell sensor as
sophisticated as a dog's nose could help distinguish people with
medical problems from healthy ones. In the United Kingdom, dogs have
already demonstrated their ability to identify people suffering from
cancer by sniffing their odors.

No one would argue that affordable, sustainable, and environmentally
sound energy is requisite for the welfare of modern civilization.
With environmental damages caused by fossil fuel pollution and the
demand for energy burgeoning worldwide, the world's energy problems
are now more urgent than ever. Alternative solutions, long debated
but rarely seriously pursued, are now being pursued with a sense of
urgency.

Further, the increasingly mobile nature of computing and
communication, and the nanonization of materials and molecular
machines, demand that smaller, lightweight, self-sustaining energy
sources be developed. An obvious source of infinite energy is the
sun. Nature has produced an efficient system to directly convert
photons into electrons and further into chemical energy; green
plants and other biological organisms have been using this system
for billions of years.

Most energy on earth is obtained from photosynthesis through
photosystems, the most efficient energy-harvesting system. If a way
to harness the energy produced by natural photosystems can be
developed, we will have a clean and nearly inexhaustible energy
source.

Borrowing from the bacterial and green plant energy-harvesting
photosystem, nanobiotechnologists have demonstrated that photons can
be converted directly into electrons by newly designed bio-solar
molecular machines. Through a combination of precision engineering
and biological engineering of the photosystem, they have constructed
an extremely high-density nanoscale photosystem and ultra-
lightweight solar-energy-harvesting molecular machines.

Two key components are required to fabricate a bio-solar energy-
harvesting molecular machine -- a bio-solar energy production system
(photosystem) from leaves of green plants, and the designed peptide
detergents. For bio-solar energy production, a simpler photosystem
was used. Scientists originally purified the photosynthesis system
from spinach, and they have recently reported successfully purifying
photosynthetic systems from maple, pine, and oak trees and from
bamboo leaves. The entire photosystem complex -- only about 20
nanometers in height -- was anchored onto a gold surface with an
upright orientation.

Experimentation is continuing to devise ways to increase the amount
and duration of energy produced by this exciting new molecular-
energy-harvesting machine.

What Lies Ahead?

The continued development of nanobiotechnology materials and
molecular machines will deepen our understanding of seemingly
intractable phenomena. Nanoscale engineering through molecular
design of self-assembling peptides is an enabling technology that
will likely play an increasingly important role in the future of
biotechnology and will change our lives in the coming decades. For
example, aging and damaged tissues can be replaced with the
scaffolds that stimulate cells to repair body parts or to rejuvenate
the skin. We also might be able to swim and dive like dolphins or to
climb mountains with a nanoscaffold lung device that can carry an
extra supply of oxygen. It is not impossible to anticipate painting
cars and houses with photosynthesis molecular machines that can
harness the unlimited solar energy for all populations on every
corner of the planet, not just for the wealthy few.

We are just at the beginning of a great journey and will make many
unexpected discoveries. Although nanotechnologists face many
challenges, they will actively pursue many issues related to the
molecular fabrication of composite materials and molecular machines.
Biotech self-assembling peptides can be considered the building
blocks for emerging materials and for fabricating future man-made
molecular machines. These peptides can also be designed in
combination to incorporate other building blocks such as sugars,
lipids, nucleic acids, and a large number of metal crystals. Nature
has inspired us and opened the door to its secrets. It is up to our
imagination to expand upon its materials and molecular machines.