Figure 1: A time-integrated image of fluorescent filaments moving along a predefined track. This
results in the spelling out of ‘Molecular Motors’1.
Nano and micro-motors have been the subject of popular culture ever since K. Eric Drexler’s
book was published in 1986 2, but Nanotechnology was actually first mentioned 27 years before
this book in Richard Feynman’s talk “There’s plenty of room at the bottom”3. Nanotechnology is
defined as technology working at the Nanoscale (1-100nm) 4. Properties of materials change when
you work on the nanoscale, and it’s these changes, and the potential new applications resulting
from these changes, which has lead to nanotechnology becoming a multidisciplinary area of research
5. This paper focuses on how rotation and translation is generated on the nanoscale across
all disciplines and how this could potentially be applied to biomedical procedures. There are
three main approaches in producing this movement on the nanoscale: biological, chemical and
physical. Biological research seeks to use self-assembled complex structures as part of the ‘bottom
up’ approach to nanotechnology 6. Particular attention is on the role of molecular motors which
are a group of active enzyme molecules that transport materials through the cell along filaments 7.
These molecular motors can produce both rotation and translation at the nanoscale and consume
chemical energy in the form of ATP to produce these actions 8. Physical research is concentrating
on using rockets and propelled motion in their research. Examples of successes so far include Janus
particles, MNRs (Micro/Nano Rockets) and fuel free motors controlled by external forces. Finally,
the chemical approach to nanotechnology is focused on using excitation of molecules to promote
ismoerization and create rotation in a molecular chain. Biomedicine is one of the many areas
hoping to benefit from advances in nanotechnology and is one of the reasons why this area is so
well funded at the moment. Even at the very beginning, in 1959 during Feynman’s talk, was the
idea of “swallowing a doctor” 3. Feynman was describing his idea of using a nanorobot that would
be capable of performing minor surgeries. Nanosurgery is just one potential biomedical application
of this research, with others including sensing and isolation, imaging and drug delivery 9. For
these ideas to become a reality, several areas of control need to be addressed. The nanomotor must
have controlled motion along specific paths, directionality along those paths, coupling to cargo
for transport, external control and steering 10. Significant progress has been made in the last
few years to control the motion of these nanomotors. A particularly impressive example is shown
in figure 1, where fluorescent actin filaments were used to spell out “molecular motors” along a
predetermined track on the micro-scale.
2.1 Biological Motors
Translation is defined as the movement of a body in a way that every point of the body moves in the
same direction and moves the same distance. In the cell, translation plays a critical role in transport
of materials and cell division. One of the proteins responsible for this in a cell is Kinesin that travels
along filaments, called microtubules, in a stepwise fashion. Microtubules are made from ? and –
tubulin that come together to form dimers. Dimers will then polymerize into protofilaments and
13 of these protofilaments then assemble to become a microtubule. Due to the nature of the dimer,
the microtubule has two distinct ends: a fast growing positive end and a slow growing negative end.
This asymmetry determines the movement of the Kinesin. To produce the stepwise movement,
Kinesin uses energy produced from the hydrolysis of ATP molecules. Kinesin plays a major role
in cell division and attention has turned towards this role for new cancer treatments. Previous
cancer drugs have been inhibitors and targeted the microtubules, which have been very successful
11. However, some concerns have been raised with these drugs as microtubules are essential for
other cell functions and some scientists are worried that the inhibitors are having an adverse effect.
New inhibitor drugs have been targeted at a specific Kinesin protein that is solely responsible for
mitosis. By targeting this protein, a more effective cancer therapy could be developed 12.
2.2 Nanorockets and Janus Particles
Inhibiting movement at the nanoscale is not the only way to enhance the effectiveness of drugs in
the body. Synthetic nanomotors have been proposed to be an ideal way to advance drug delivery in
the body. Translation from synthetic nanomotors can be split into four main areas, depending on
the propulsion system they employ. Propulsion systems currently used in nano research are self-
electrophoretic, bubble, ultrasound and magnetic. Self-electrophoretic propulsion uses a proton
concentration gradient to drive fluid and create the motion for the motor, known as a catalytic
nanowire motor 13. Unfortunately at the moment this propulsion is not compatible with biological
fluids due to their high ionic strength, so will not be discussed in detail in this report 14. Bubble
propulsion has been used in nanotechnology in two ways: Janus particles and nanorockets. Janus
particles are particles containing two materials with different chemical properties on each side.
Casagrande created the first Janus particle in 1988, with one side of the particle hydrophobic and
the other hydrophilic 15. Janus particles can be used to produce bubbles to propel the particle
through the reduction of hydrogen peroxide to hydrogen gas. Recently, Gao et al. have developed
the first water driven Janus particle made from an aluminium alloy16. The particle is partially
covered by a titanium layer, with the exposed aluminium layer reacting with water, as shown in
figure 2. The particles are fabricated as shown in figure 3, by pushing two slides containing liquid
gallium and aluminium together to form an alloy. The exposed side of the particles is then coated
with Ti using e-beam evaporation.
Figure 2: A representation of a water driven Janus particle. The dark hemisphere is the Al-Ga
alloy and the green layer represents the nonreactive Ti coating. The chemical equation for the
reduction of water is shown 16.
Bubble propulsion has also been used to generate translation-using nanorockets. Taking inspi-
ration from success in the 20th century with macro scale rockets, nanoscale rockets are conical in
their design and can reach very high relative velocities 17. Nanorockets have different problems to
Figure 3: A diagram showing the step-wise fabrication of the water driven Janus particle: (a)
shows the two separate layers of aluminium particles and liquid gallium, in (b) the layers are
pushed together to form the alloy, (c) shows the removal of the top slide, (d) shows the coating
of one side of the particle with a non reactive Ti layer through e-beam evaporation and (d) shows
the final particles after being separated with sonication16.
overcome than their macroscopic counterparts due to the difference in Reynolds numbers (typically
105 to 108 in macro scale rockets and can be as low as 10 5 in nanorockets) 17. Reynolds numbers
are dimensionless numbers that give a ratio of inertial to viscous forces, so at the nanoscale viscous
forces will dominate. These nanorockets are powered by a chemical reaction on the inside of the
conical design, taking in fuel from the surrounding medium at the front and expelling bubbles at
the rear to propel the rocket forward. This is shown in figure 4.
Nanorockets are engineered in two ways: strain engineering and template electro-decomposition.
Strain engineering was used to manufacture nanorockets for the first time in 2008 by Mei et al.
and takes advantage of a difference in thermal expansion coefficients of different metal layers
18. The metal sheets are layered on selectively to ensure a nonreactive outer layer, with the
support selectively etched away causing the metals to spontaneously roll and form a conical shape.
Alternatively template electodecomposition can be used. This technique deposits metal layers
sequentially into a template, which is then dissolved to leave a conical rocket shape 19. Similar to
Janus particles, the most commonly used fuel for nanorockets is hydrogen peroxide. Gao et al. have
recently used a zinc layer in their nanorocket designs that can react with an acidic environment
to produce the hydrogen bubbles required 20. Now that both Janus particles and nano-rockets
can be used without the use of hydrogen peroxide as a fuel source, the biomedical applications
of this technology is becoming closer to a reality. A few challenges still remain for translational
nanotechnology before it is used for biomedical applications; namely to control the speed and
direction of the rockets and particles. In this regard, Solvev et al have showed magnetic control of
a nanorocket including loading, transportation and delivery of objects 21. By functionalizing the
outside of the rockets, antibodies could be attached and then be taken directly where they need
to be. This could revolutionize drug delivery. It even could be used for imaging, by dropping a
molecule into a part of the body, which could not be accessed by other means.
Figure 4: A diagram of the micro/nanorocket showing the fuel entering through the hole at the
tip of the rocket, which then reacts chemically with the inner layer to produce hydrogen bubbles
producing a forward thrust 17.
3.1 Biological Rotation
Rotation is the movement of an object around a fixed point, caused by a force not acting through
the centre of mass of an object. The most well known, and the inspiration for a lot of synthetic
rotational motors, is the ATP synthase 22. The ATP synthase consists of two regions, F0 and F1.
F0 is hydrophobic and sits in the lipid membrane layer, whereas F1 is hydrophilic. In a cell, there
is a difference in concentration of hydrogen ions either side of the membrane causing a potential
energy gradient. This potential energy gradient causes the protons to flow through F0, causing
F1 to rotate and synthesize ATP from ADP and Pi 23. ATP is used to store the energy living
cells need to grow, move and repair. ATP synthase is present in all living organisms, but the
complex nature of the structure led Anandakrishnan et al. to question whether this is the most
efficient mechanism for this process of producing ATP. They studied a wide range of other possible
mechanisms and found that this rotary mechanism is faster than the alternatives and particularly
good with preforming under low energy conditions 24. As mentioned above, ATP synthase is
present in all living organisms, including pathogenic bacteria. Certain strains of bacteria can enter
dormant states while inhabiting parts of the body (e.g. the lungs) when dealing with low energy
conditions and become very resistant to current antibacterial medicine 25. Lu et al. hopes that by
gaining a greater understanding of this rotational biomotor, the ATP synthase in bacteria can be
targeted with specific antibacterial drugs, which could combat diseases like tuberculosis. The ATP
synthase is a self-assembled biorotor that hasn’t been able to be replicated by synthetic means so
far. Instead of trying to build rotors from protein building blocks, attention has turned to using
cells that are already mobile to provide the energy for a man made rotor. An example of this is the
mycoplasma mobile. This is a species of gliding bacteria that move constantly over solid surfaces,
reaching speeds of up to 7 ?m/s, transporting items up to 10 times its own size and exerting forces
of up to 27 pN 26. These properties have been used by Hiratsuka to power a microrotor shown in
A rotor, made from SiO2 is placed onto a Si track and bound to the mycroplasma mobile using
biotin–streptavidin interactions 27. By introducing the bacteria asymmetrically, rotation in one
direction is ensured. The application of nanotechnology powered in this way by gliding bacteria
is still some way off being realized. Hiratsuka et al believe the future of this nanomachine is in
genetically modifying the current bacteria to gain greater control of its properties27. In their
paper, modifying the surface proteins to load (and unload) cargo would be greatly beneficial. Also
considered is to introduce a regulatory system that would allow the switching on and off of the
Figure 5: Diagram showing the micro-rotor driven by the gliding bacteria mycoplasma mobile.
The rotor is made from a SiO2, which is fitted onto a Si track. The cells are placed onto the
track walls asymmetrically to ensure unidirectionality. The cells are attached to the rotor by using
movement of the bacteria.
3.2 Chemical Rotation
Rotation isn’t just generated at the nanoscale through biological motors, it can also be generated
through the rotation of a molecule chain. Browne et al. describe how three criteria must be met in
order to build a completely synthetic rotor. Firstly it must have controlled directionality. Secondly
it must have a way to consume energy and have an energy source. Finally it must have repetitive
360 rotation 28. Koumura et al. have met this set of criteria in their design shown in figure
6 29. The design consists of two identical halves linked by a carbon – carbon double bond at
the centre. By introducing light to the system, isomerization from cis to trans (or the reverse)
takes place causing a 180 rotation. This isomerization leads to the unstable formation of the
large functional groups attached to the central carbons. These unstable groups will then undergo
thermally controlled helicity inversion which will cause the groups to relax into new positions,
but block the backwards rotation 29. Another addition of light energy will then cause another
180 rotation through isomerization. Crucial for rotation to occur in this way is the functional
groups attached to the central carbons as they determine the speed and direction of the rotation.
Kudernac et al. have taken this idea further and effectively built a molecular car based on these
designs, which is able to translate as a result of rotation on the nanoscale30.
Figure 6: Diagram showing the four stages to the 360 rotation of (3R,30R)-(P,P)-trans-
1,10,2,20,3,30,4,40-octahydro-3,30-dimethyl-4,40-biphenanthrylidene (number 1 in the figure). The
molecule is exposed to UV radiation that forces an isomerization from trans to cis. Thermal
relaxation then means the bulky functional groups cannot rotate back to the original molecule.
Further radiation causes another 180 rotation and another thermal relaxation occurs29.
Generating rotation and translation on the nanoscale has been an ongoing field of research since
1986 and continues to be an area of research that secures heavy investment. The potential ap-
plications of nanotechnology are wide ranging, with particular importance in biomedicine. This
has lead to a multidisciplinary area of research. This includes; biologists looking at molecular
motors such as Kinesin to translate items at the nanoscale, powered by ATP; physicists using their
knowledge of rockets to produce translation on the nanoscale in the form of Janus particles and
nanorockets, powered by chemical reactions; and chemists have been looking at the rotation of
molecules about a carbon-carbon double bond in response to light, even going as far as producing
a nanoscale car. The nanotechnology being developed could be used to enhance drug delivery,
help with imaging the body and detection of unwanted molecules in the body. In short, it has the
potential to revolutionize the biomedical field.