IN ACTION

BIONANOMACHINES

BIONANOMACHINES IN ACTION 12/14/23

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• As you read these words, 10,000 different nanomachines
are at work inside your body. These are true
nanomachines

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• Each one is a machine built to nanoscale specifications,
with each atom precisely placed and connected to its

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neighbors.

• The human body is arguably the most complex

mechanism known to the universe, and most of the
action occurs at the nanoscale level.
• These nanomachines work in concert to orchestrate the
many processes of life—eating and breathing, growing 2
and repairing, sensing danger and responding to it, and
reproducing etc.
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• Remarkably, many of these nanomachines will still

perform their atomsized functions after they are isolated

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and purified, provided that the environment is not too
harsh.

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• They do not have to be sequestered safely inside cells.
Each one is a self-sufficient molecular machine. Already,
these nanomachines have been pressed into service.
Natural digestive enzymes like pepsin and lysozyme are
so tough that they can be added to laundry detergent to
help digest away stains.
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• The bionanomachines made by living cells. They are different
from the machines in our familiar world in many ways. They
have been developed by the process of evolution (instead of
intelligent design),which places unfamiliar restrictions on the

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process of design and the form of the final machine.

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• Bionanomachines are also selected to perform their tasks in
a very specific environment and are subject to the unfamiliar
forces imposed by this environment. We must keep these
differences in mind when trying to understand natural
biomolecules, and we must keep these differences in mind
when we use these natural bionanomachines as the starting
point for our own bionanotechnology. 4
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• The entire field of genetic engineering and biotechnology is
made possible by a collection of DNA-manipulating
nanomachines, now available commercially. In general, natural
bionanomachines are remarkably robust.

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• Bionanomachines are made by living cells. They are different

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from the machines in our familiar world in many ways. They
have been developed by the process of evolution (instead of
intelligent design), which places unfamiliar restrictions on the
process of design and the form of the final machine.

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 Bionanomachines are also selected to perform their tasks

in a very specific environment and are subject to the
unfamiliar forces imposed by this environment. We must

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keep these differences in mind when trying to understand
natural biomolecules, and we must keep these differences in

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mind when we use these natural bionanomachines as the
starting point for our own bionanotechnology

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THE UNFAMILIAR WORLD OF BIONANOMACHINES

Biological machinery is different from anything we build with our

familiar, human-sized technology.

Natural biomolecules have organic and often unbelievable shapes,

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unlike the tidy designs of toasters and tractors.

They perform their jobs in a foreign environment, where jittery thermal

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motion is constantly pushing and pulling on their component parts.

They are held together by a complex collection of bonding and

nonbonding forces.

At their small scale, bionanomachines are almost immune to the laws
of gravity and inertia that dominate our machines. The world of
bionanotechnology is an unfamiliar, shifting world that plays by different
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rules.
THE UNFAMILIAR WORLD OF BIONANOMACHINES

Gravity and Inertia are Negligible at the

Nanoscale

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Nanomachines Show Atomic Granularity

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Thermal Motion is a Significant Force at
the Nanoscale

Bionanomachines Require a Water

Environment 8
Gravity and Inertia are
Negligible at the
Nanoscale

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Gravity and Inertia are Negligible at the Nanoscale

 Macroscopic objects, like bicycles and bridges,

are dominated by the properties of mass. For

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centimeter-sized and meter-sized objects,
physical properties

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 such as friction, tensile strength, adhesion, and
shear strength are comparable in magnitude to
the forces imposed by inertia and gravity.

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Gravity and Inertia are Negligible at the Nanoscale

Mass increases with the cube of the size of an

object, and properties such as strength and

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friction increase linearly or with the square of
size.

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 The increase in inertia or weight can quickly
overcome the increase in strength in a large
structure such as a building.
These scaling laws are quite familiar, and it is
common sense to add extra support as we build
larger and larger structures. We do not expect to 11

be able to build a skyscraper a mile tall.

Gravity and Inertia are Negligible at the Nanoscale

 These scaling laws also apply in the opposite

direction, with the opposite effect as we go to

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smaller and smaller machines. Micrometer-sized
objects, like individual grains of sand or

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individual cells, already interact differently from
macroscopic objects.

Inertia is no longer a relevant property, so our

intuition may lead to inappropriate conclusions.
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 Gravity and Inertia are Negligible at the Nanoscale

 E. M. Purcell described the surprising properties of

bacterial cells swimming in water. These cells use a
long corkscrew-shaped flagellum to propel

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themselves through the water. When the cell stops

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turning the flagellum, we might expect that the cell
would slowly coast to a stop, like a submarine does
in the ocean.
However, because of the inertia scales differently
relative to the viscous forces within the
surrounding water, the cell actually stops in
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less than the diameter of an atom.
Gravity and Inertia are Negligible at the Nanoscale

 Gravity is also a negligible force when dealing with small

objects. The actions of small objects are dominated by their
interaction with neighboring objects. The molecules in

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water and air are in constant motion, continually battering
small objects from all sides. So, fine dust stays suspended in
the air instead of dropping quickly to the floor, and objects

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in water, if you look at them with a microscope, undergo
random Brownian motion.

 The attractive forces between small objects are also

stronger than the force of gravity. Water droplets can hang
from the ceiling because of these attractive forces.
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Nanomachines Show Atomic Granularity

 Nanoscale objects are built of discrete combinations of atoms

that interact through specific atom-atom interactions. We
cannot design nanomachines in a smoothly graded range of

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sizes. They must be composed of an integral number of
atoms. For instance, we cannot design a nanoscale rotary
motor

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Biological nanomachines are nano-sized tools used for the
monitoring, diagnostic, and treatment of disease at the
molecular scale. Biological nanomachines adopt the structure
and communication principles of natural biological cells. From
a communication engineering perspective, bionanomachines are
computational devices that work at a nanoscale to perform

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simple functionalities like environmental sensing to more
complex functionalities like actuation and manipulating the

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environment (i.e., human body).
These devices have limited computation power and memory
due to their nano size. Yet, their minute size is an edge for
many novel applications, as they can be concealed and
implanted in hard to access areas (such as deep inside the tissue
of the human body) in a non-invasive manner. These machines
are non-invasive and are made up of biodegradable material. 17
The Role of Biological Nanomachines in Pervasive
Healthcare
Bionanomachines are resource-constrained devices and cannot
perform complex tasks alone. Thus, bionanomachines
communicate with each other to share information and execute
designated tasks, forming a ‘biological nanonetwork’.

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Nanonetworks are envisioned to lead the world to a sophisticated
healthcare experience. With the nanosensors and micro-robots
patrolling inside the human body to collect physiological

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parameters, there is no need to go to labs to draw blood samples
and wait for results.
If nano actuators are connected to the nano \sensors, they can
repair the detected malfunctioning in the body there and then.
Biological nanomachines promise maximum therapeutic effects
with very limited adverse effects. Other macro-scale therapeutics
like chemotherapy not only kills the cancerous cells but also 18
destroys the healthy cells of the human body. Whereas,
nanotechnology-based TDD only targets the tumor sites.
The potential benefits of nanonetworks can be increased when
they are connected to external networks such as the internet.
Connecting in body network with external networks enables
pervasive healthcare, where a healthcare provider can monitor the
patient remotely from the comfort of their home.

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The healthcare provider can demand physiological parameters like
Blood pressure, glucose, ECG at any time, and can administer
commands according to received parameters remotely.

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Additionally, after the recent pandemic of Covid-19 and the
lockdown regime, there has been an accelerated interest in
exploring remote therapeutic

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 Architecture of Bionanomachines
Nanomachines can be fabricated using novel nanotechnology material (i.e.,
like carbon nanotubes and graphene nanoribbons) and by reprogramming
biological materials like cells, viruses, bacteria, bacteriophage, erythrocytes,
leukocytes, and stem cells or by artificially synthesizing biomolecules like
liposome, nanosphere, nanocapsule, micelle, dendrimer, fullerene, and
deoxyribonucleic (DNA) capsule.

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Certain design and development factors must be considered during the
fabrication of nanomachines. These factors include the size, shape, stability,
and biodegradability of the system.

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In biomedical applications, nanomachines are introduced into the blood vessels,
from where they traverse to their targeted location. The smallest blood vessel is
a capillary that is 5-10 micrometer in size; hence the upper bound of
nanomachines must be set accordingly.
On the other hand, nanomachines that are less than 5nm can be easily filtered
out by kidneys. Thus, the size of the nanomachine must be propped. Channel
characteristics like blood vessel geometry, elimination, adhesion, reaction,
extracellular viscosity must be taken into account as well while fabricating 20
nanomachines.
Components of Nanomachines

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A bionanomachine is comprised of several hardware constituents. All the software and
programming of the nanomachine is included in the information processing unit. The
components of nanomachine are presented below:
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 Information Processing Unit
The information processing unit contains the programming part of
nanomachine, which interprets command and process data. The
functionality and behavior of nanomachine are coded in this unit. The
information processing unit is capable of performing only trivial
operations, like Boolean operations using only one transistor.
Information processing unit for nanomachines is made up of nano-sized

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transistors like a single atom or quantum dots. Researchers
from Lawrence Berkeley National Laboratory have provided a proof of

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concept for the smallest transistor which has a gate length of just one
nanometer. The processing unit is analogous to the nucleus of the cell.

Power Unit
Biological cells already exhibit the natural behavior of energy
harvesting. A component of the biological cell called mitochondria 22
releases Adenosine Triphosphate (ATP) as a chemical energy
supply to charge the cell
Communication Unit
Communication is the basic functionality in any network,
Likewise, the communication unit defines its capability of
nanomachine to communicate with the environment.
Nanomachines react in response to external stimuli produced by
other nanomachines. To accomplish this, gap junctions located

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on the outer surface of the cell enables communication with the
extracellular environment.

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Memory Unit
The memory unit is narrowly associated with the information processing unit.
Nanodevice needs a memory unit to store sensed data or memory can be used for some
configuration and instruction set to be executed. Some nanomachines might not require
memory at all because nanomachines are not supposed to perform complex
computations. The nucleus of the cell can act as a long-term memory unit and the
cytoplasm can perform the short-term memory functionality.

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Sensors and Actuators
Sensors continuously interact with the environment by collecting the chemical,
physical and biological changes in the environment. Actuators work closely with the
sensors by manipulating the environment in response to the sensed data. In biological
cells, sensing is done by a natural process like ligand-receptor binding, or cilia can be
used as a sensing antenna. Gap junction channels are used for actuation

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Locomotion Unit
Locomotion is the ability of nanomachines to move around in the environment. The

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locomotion can be passive via molecular diffusion into the environment or active via
molecular motors.

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Visualizing the bionanomachines that create potent antibiotics
and other modern drugs

Nonribosomal peptide synthetases (NRPSs), create

potent antibiotics, immunosuppressants and other
modern drugs.

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“NRPSs are really fantastic enzymes that take small
molecules like amino acids or other similar sized

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building blocks and build them up to natural,
biologically active, potent compounds, many of which
are drugs,” (May 2020 issue of
Nature Chemical Biology,).

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An NRPSs works like a factory assembly line that consists of a
series of robotic workstations.
Each station has multi-step workflows and moving parts that
allow it to add one building block substrate to the growing
drug, elongating and modifying it, and then passing it off to the
next little workstation, all on the same huge enzyme.

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Bionanomachines: Proteins as resistance fighters

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Fluorescent image of single motor proteins (left): Motion of two diffusing kinesin
molecules (green) on a microtubule (red) shown as a time series kymograph.
Schematic (right): By dragging diffusing kinesin molecules with laser tweezers over a 28
microtubule, the friction force between the motor and its microtubule track can be
measured very precisely
Friction limits the speed and efficiency of macroscopic engines. Is this also
true for nanomachines? A Dresden research team used laser tweezers to
measure the friction between a single motor protein molecule and its track.
The team found that also within our cells, motors work against the resistance

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of friction and are restrained in its operation -- usually by far not as much
though as their macroscopic counterparts. These first experimental
measurements of protein friction could help researchers to better understand

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key cellular processes such as cell division which is driven by such
molecular machines

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Friction is the force that resists the relative motion of two bodies
in contact. The same is true on the nanoscale: Molecular motors
have to fight the friction created between them and their tracks.
However, since the frictional forces acting on such motors had
not been measured before, it was not known how they depend on
the speed and the direction of motion.

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Efficient nanomachines
Protein friction also gives insight into the efficiency of kinesin.
"About half of the energy from the motor’s fuel ATP is dissipated

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as friction between the motor and its substrate" Howard
comments. Schäffer adds: "What remains after further dissipation
inside the motor is used for mechanical work—the efficiency is
usually much better than for man-made machines". The dissipated
energy is eventually converted to heat, that contributes to the
heating of our body. Thus, for example our muscles are partly
heated by protein friction as the muscle motor proteins do their 30
work.
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