Running Head: BACTERIA BASED NANOMACHINES

Bacteria Based Nanomachines

Nano Report: Nanomachines Richard A. Sitterley

Excelsior College Introduction to Nanotechnology

Running Head: BACTERIA BASED NANOMACHINES Abstract This report explores the development of nanomachines that are based on the anatomy of bacteria.

Specific advantages of using the bacterial model are addressed, as well as specific challenges faced by bacteria-sized objects in the human body. The primary focus of this papers is on bacteria based nanomachines designed to function inside the human body. Brownian motion is explained, from a basic standpoint, in its relevance to nanosized objects in an aqueous environment. The flagellum propulsion system used by bacteria such as E. Coli is also covered, describing its basic components and their natural bottom-up assembly. A top-down approach to designing Artificial Bacterial Flagella (ABFs) is introduced as well, noting similarities and differences of these devices to real bacteria.

Running Head: BACTERIA BASED NANOMACHINES

Introduction One approach to designing nanoscale machines is to model their design based on bacterial anatomy. An initial question that one may ask, considering all of the existing methods of mechanical and robotic engineering that have developed over time, is Why model nanomachines from bacteria? As an example of this thought process, one may consider that modern technology has some very effective designs for submarines. Considering this, one may ask why we do not simply miniaturize this machine to micron sized proportions. From a basic standpoint, this initially may seem like a good strategy for building a nanomachine. However, the existing model of a normal submarine simply could not function at a microscopic size, even if all of its nanosized components were properly designed and functional. We will return to the submarine comparison later in this report, but for now it will suffice to say that nanomachines are affected by different forces and principles than larger machines that we are familiar with. The bacterial model for nanomachines makes sense because, from a certain perspective, bacteria are basically a functional nanomachine created through natural processes. Bacteria, which were among the first living oranisms to inhabit the earth, have evolved for millions of years. As such, they have developed effective means of propulsion, reproduction, and cross communication that has proven effective for objects of their size. This paper will focus on bacteria-based nanomachines intended to operate inside the human body.

The Bacteria-Based Approach

Advances in microbiology over the years has allowed a rather thorough understanding of many types of bacteria. Scientists now have a firm grasp on certain mechanisms used by bacteria to navigate

Running Head: BACTERIA BASED NANOMACHINES through their environment and perform their unique functions. Some common bacteria, such as E. Coli, are very well understood and documented through extensive research conducted on them for many years (Jones, 2008). Health related concerns with E. Coli have driven further research on this bacteria so that we can better prevent and treat E. Coli bacteria infection in humans. However, these

efforts have also provided information that is useful to scientists for designing nanomachines modeled after these bacteriia. Just as the wagon wheel helped inspire the use of wheels for automobiles, bacteria are a source of inspiration for designing nanomachines.

To some, it may seem odd to design a machine that will operate within the human body, and model this machine from bacteria which are generally considered harmful and infectious to humans. To many scientists, it is the efficiency at which bacteria are able to invade our bodies that makes them the ideal model for a nanomachine. Although bacteria often serve a harmful purpose in the body, this purpose can be modified to help us. It is relevant to mention that bacteria are already being used for helpful purposes in water treatment, solar cells, fuel production, and medicine. Within our own bodies, bacteria also aid in the digestive process, breaking down minerals, and making essential vitamins. As nanotechnology continues to advance, scientists hope to design nanomachines that can perform a variety of helpful functions from inside our bodies.

Identified Challenges

From a nanoscale perspective, oil, water, and other water based fluids should not be considered freeflowing, as nanoparticles encounter a great deal of high impact collisions and mass obstructions while immersed in fluids (Jones, 2008). Inside the human body, and more precisely the fluids that flow through it, is an environment that is dominated by high viscosity. Viscosity of the surrounding medium

Running Head: BACTERIA BASED NANOMACHINES plays a much bigger role for smaller particles than for larger ones, which is also the case for any conceptual nanomachine we may try to build. Nanoscale objects exhibit a type of constant vibratory

motion, which is considered random in nature, due to the multitude of forces that influence objects of such small mass and size (Jones). This is commonly known as Brownian motion, and to a nanoparticle, Brownian motion is every bit as significant as gravity is to larger objects. Brownian motion is complex, influenced by heat, viscosity, van der Waals forces, and other factors. For the scope of this report, it is sufficient to state that Brownian motion affects the motion of small particles through constant random collisions with other particles that make up the surrounding medium (Jones, 2008).

If we are to succeed at creating a machine that is the size of a bacterium, we must understand the primary forces that affect bacteria and influence their design. In the human body, the fluid mechanics affecting the propulsion of microbes is extremely different from fluid mechanics that influence the design of boats, submarines, and other watercraft. If scientists could somehow shrink a submarine and all of its working components down to the size of a bacterium, it would have no ability to steer or propel itself through the human body as bacteria can. The body's fluids are generally water-based, and as such their viscosity is relatively close to that of water. The reason our miniature submarine could not propel itself is because, at normal scale, the primary force resisting the motion of a submarine is inertia, while at the microscopic and nanoscopic scale, this primary impeding force is the viscosity of water (Jones, 2008). Common water propulsion systems like those used to propel a submarine are not designed to overcome such a highly viscous environment, which is comparable to moving through a surrounding medium that is thicker than cold honey. The viscosity of the water does not truly change, of course, but it is important for us to understand that water feels a million times more viscous to bacteria than it does to us. Over time, bacteria have developed propulsion systems that allow them to affectively travel through fluids. Careful study of bacteria have helped scientists discover that twisting

Running Head: BACTERIA BASED NANOMACHINES rotary mechanisms are one of the more effective means of propulsion for nanosized objects in environments of high viscosity (Jones).

Ideal Propulsion System

Scientists have a good understanding of E. Coli, and it is well understood that E. Coli use a type of rotary motor to propel themselves through fluids (Jones, 2008). This motor, embedded in the cell wall, is driven by energy obtained from hydrogen ions (Jones). This biochemical rotary motor turns a long, whip like structure in a spiraling motion that propels the bacteria through fluids (Whitesides, 2001). This structure, known as a flagellum, is made up of various self-assembled proteins called flagellin (Applegate, 2010). This entire biochemical motor's structure, consisting of over forty basic components is, in fact, constructed via self-assembly (Applegate). This is an inspiration to many scientists in the field, as it demonstrates the potential of self-assembly in creating complex machines. The most basic components of a flagellum propulsion system, starting at its base, are the stator, rotor, hook, junction, and filament (Applegate). Although the flagellum structure is quite complex, understanding these primary components serves as a good starting point when attempting to build a similar nanoscale device. If scientists can master the basic design of this mechanism, future developments may lead to even more advanced features based on the bacterial structure. For example, if the flagellum of a bacterium breaks, it can be regenerated through self assembly of proteins continuously moving through the central channel of the flagellum (Applegate). As we gain a better understanding of nanomaterials and self-assembly, we may one day have the ability to design nanoscale machines with this level of complexity.

Running Head: BACTERIA BASED NANOMACHINES

Internet Research

Internet research on bacteria based nanomachines indicates some significant progress in successfully producing functional nanoscale devices modeled from bacteria. At the Institute of Robotics and Intelligent Systems at ETH Zurich, researchers have designed small devices modeled from E. Coli that can travel through fluids using a flagellum-like structure (Medical Micro-robots, 2009). These devices, called Artificial Bacterial Flagella (ABFs), currently measure about ten micrometers in length (Medical Micro-robots). Actual E. Coli bacteria are about two micrometers long by one-half of a micrometer in width. As the technology improves, scientists expect to design ABFs that are just as small as E. Coli, if not smaller. The devices are constructed from indium, gallium, arsenic, and chromium materials which are deposited on a substrate using vapor deposition techniques (Medical Micro-robots). The ABF is then patterned from the deposited materials using lithography and etching techniques, which produces a long narrow ribbon-like structure from the deposited materials. Upon detachment from the substrate surface, the ribbon automatically curls into a spiral, due to interactions between the molecular lattice of the different deposited layers (Medical Micro-robots). This artificial flagellum is then attached to a magnetic head, constructed from vapor-deposited chromium, nickel, and gold (Medical Micro-robots). The nickel content allows the head of the ABF to be affected by an external magnetic field, which is the intended guidance mechanism for these devices. Using a rotating magnetic field generated by several coils, these ABFs can be directed forwards, backwards, upwards, downwards, and rotated in any direction (Medical Micro-robots). This guided control is achieved by adjusting the strength and direction of the externally induced magnetic field. They travel at a speed of about twenty micrometers per second, which almost as fast as E. Coli, whose speed is about thirty micrometers per second (Medical Micro-robots). The speed of ABFs is also expected to improve.

Running Head: BACTERIA BASED NANOMACHINES

These ABFs are designed with biomedical applications in mind. Although ABFs are at a very early stage in development, researchers hope to use them in the future to deliver drugs to specific places in the body, clean plaque from arteries, and manipulate cellular structures in ways that would otherwise be inaccessible or require dangerously invasive surgery to access. Despite the recent accomplishments in ABF technology, researchers have a long way to go if they hope to produce nanomachines that are as sophisticated as E. Coli. First of all, these existing ABFs only consist of two components, compared to forty or so components that make up a true flagellum propulsion structure. Secondly, the ABF is rigid, which limits its efficiency. Bacterial flagella are flexible, composed of self assembled proteins with regenerative capability. Furthermore, bacterial flagella are self-propelled and do not require external forces to guide them to a target. Perhaps the biggest limitation to producing ABFs that are comparable to real bacteria is that ABFs are made using top-down methods, while nature creates bacteria through bottom-up assembly. Improvements in bottom-up nanoscale production methods could pave the way for more advanced ABFs. Conclusion

In conclusion, the bacteria provide an effective model for designing nanomachines with an intended function inside the human body. However, many functions and structural details of bacteria are still unknown, and as we learn more about bacteria we can also gain useful information that may aid the design of more functional nanomachines. Top-down production methods are a limiting factor in producing bacteria based nanomachines. As bottom-up production methods develop, we can expect to see nanomachines with more complexity on a smaller scale. Even with existing production methods, it appears that we are very close to seeing nanomachines playing an active role in biomedical applications, which may dramatically change how we diagnose and treat many diseases.

Running Head: BACTERIA BASED NANOMACHINES

Bibliography

Jones, R. (2008). Soft Machines: Nanotechnology and Life. New York, NY: Oxford University Press.

Whitesides, G. (2001). The Once and Future Nanomachine. Scientific American, September 16, 2001. Retrieved from http://www.ruf.rice.edu/~rau/phys600/whitesides.htm

Turco, G. (2010). Nanobots Are Coming! Nanobots Are Here! Depth of Processing Retrieved from http://depthofprocessing.blogspot.com/2010/09/nanobots-are-coming-nanobots-are-here.html

ETH Zurich (2009). Medical Micro-robots Made As Small As Bacteria. ScienceDaily. Retrieved from http://www.sciencedaily.com/releases/2009/04/090418085333.htm

Applegate, K. (2010). Self-Assembly of the Bacterial Flagellum: No Intelligence Required. The Biologos Forum. Retrieved from http://biologos.org/blog/self-assembly-of-the-bacterial-flagellum-no-intelligence-required