M13 virus used as building blocks for biomaterials

Biomaterial is any matter, surface, or construct that interacts with biological systems. Biomaterials can be produced either naturally or synthesized in the laboratory using a variety of chemical processes utilizing metallic, polymeric or ceramic components. They are often used and/or adapted for many medical applications, and thus comprise whole or part of a living structure or even a biomedical device which performs, augments, or replaces a natural function.

Biomaterials are used in very important medical activities like joint replacements, bone plates, bone cement, artificial ligaments and tendons, dental implants for tooth fixation, blood vessel prostheses, heart valves, skin repair devices (artificial tissue), cochlear replacements, contact lenses, breast implants etc.

Biomaterials must be compatible with the body and  issues of biocompatibility must be resolved before a product can be placed on the market and used in a clinical setting.

M13 virus
 virus is a filamentous bacteriophage composed of circular single stranded DNA (ssDNA) which is 6407 nucleotides long encapsulated in approximately 2700 copies of the major coat protein P8, and capped with 5 copies of two different minor coat proteins (P9, P6, P3) on the ends. The minor coat protein P3 attaches to the receptor at the tip of the F pilus of the host Escherichia coli. It is a non-lytic virus. M13 plasmids are used for many recombinant DNA processes, and the virus has also been studied for its uses in nanostructures and nanotechnology.

Turning M13 virus into most important structural proteins in nature
Researchers, led by Seung-Wuk Lee, associate professor of bioengineering , UC Berkeley and faculty scientist at Lawrence Berkeley National Laboratory (LBNL), have turned a benign M13 virus into an engineering tool for assembling structures that mimic collagen, one of the most important structural proteins in nature. This process they developed could eventually be used to manufacture materials with tunable optical, biomedical and mechanical properties such as cornea, teeth and skin.

The researchers chose the M13 virus which is harmless to humans and a model organism in research labs – because its long, “chopstick-like” shape with a helical groove on its surface closely resembling collagen fibers.

The technique the scientists developed entails dipping a flat sheet of glass into the viral bath,...

then slowly pulling it out at precise speeds. The sheet emerges with a fresh film of viruses attached to it. At a pulling rate ranging from 10-100 micrometers per minute, it could take 1-10 hours for an entire sheet to be processed.

By adjusting the concentration of viruses in the solution and the speed with which the glass is pulled, the researchers could control the liquid’s viscosity, surface tension, and rate of evaporation during the film growth process. Those factors determined the type of pattern formed by the viruses. The researchers created three distinct film patterns using this technique.

With a relatively low viral concentration of up to 1.5 milligrams per milliliter, regularly spaced bands containing filaments oriented at 90 degree angles to each other were formed.

The most complex pattern – described as “ramen-noodle-like” by the researchers – was formed using viral concentrations ranging from 4-6 milligrams per milliliter. By using the Advanced Light Source at LBNL, the researchers discovered that this highly ordered structure could bend light like a prism in ways never before observed in nature or other engineered materials.

Aligning collagen in a perpendicular, grid-like pattern creates transparency, and is the basis of corneal tissue. And corkscrew-shaped fibers, mineralized after interacting with calcium and phosphate, can generate the hardest parts of our body: bones and teeth. However, observed Lee “Unfortunately, collagen is a difficult material to study because it is hard to tune its physical and chemical structures. We needed a convenient model system to solve this problem.”

The team members believe their model approaches the way nature can dynamically change environmental variables when building tissues. They also demonstrated that their engineered films can serve as biological substrates. For future research, there are many opportunities for this technique, for example in the area of tissue regeneration and repair.


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