Genetic-engineered cells works as mortar for intelligent structures, says S.Ananthanarayanan.
The Cuckoo Clock, the printing press, the steam engine, the digital computer, are constructs of hard and soft material, ingeniously put together, so that they act like they possess intelligence. Could the functionality of things be built into the very material that objects are made up of?
The architect-artist Haresh Lalwani imagines structures that shape themselves with intelligence, and adapt to the environment, like living things. And on the way to thinking of a DNA of form, he devises objects and shapes that grow into their function and purpose. But each one stays unique, like individuals of a living species.
Anna M. Duraj-Thatte, Avinash Manjula-Basavanna, Jarod Rutledge, Jing Xia, Shabir Hassan, Arjirios Sourlis, Andrés G. Rubio, Ami Lesha, Michael Zenkl, Anton Kan, David A. Weitz, Yu Shrike Zhang and Neel S. Joshi, from Harvard and North-eastern Universities and Brigham and Women’s Hospital, Harvard Medical School, report a development that seems to actualize Lalwani’s dream. Writing in the journal, Nature Communications, the authors describe a technique of building objects with a functional, living material, which can then carry out a purpose and maintain itself.
A development of recent years has been the technique of 3-D printing, as a step of progress beyond 2-D printing. The older process is nothing but automated positioning dyes on a surface, to create text or images in two dimensions. For creating objects, not just images, we need material in bulk, not just a dye on a surface. One way of shaping objects, known since long, has been chiseling or carving. In its modern form, this is shaping material on a lathe. And with the computer-controlled lathe we can automate the process, converting just numerical data, a ‘programme, into a 3-D form.
This process, however, is not ‘printing’ of the object, in the sense that this is a case of ‘shaving away’ and reducing existing material to the desired shape. In two dimensions, this would be like covering a page with ink and then erasing the parts where the text is not to appear. For 3-D printing, what we need is to deposit material, layer by layer, and build up the desired object from scratch, rather than come down to the object from a larger block of material.
The 3-D printer does just this, using special materials, which can be deposited and would stick, to finally take the shape desired. And the depositing is computer controlled. And like automatic lathes are able to shape objects according to computer drawings, the 3-D printer can also take its instructions from designing software. In its early stages, 3-D printing could create just a look-alike, albeit speedily, and it was known as rapid prototyping. But the process has evolved and is now used to manufacture complex shapes that are not feasible in the normal way.
A development of 3-D printing is 3-D bioprinting – where what is built up is not just an object with a given shape, but a shape built of living cells. An application of this method is to use cells to generate living tissue, or even organs, which is useful in studying the efficacy of drugs. And another application is in creating scaffolds, which can be implanted to support the natural regeneration of body tissue. The paper by the Harvard group mentions applications that interconnect a kind of bacteria, which participate in photosynthesis, to create a surface that generates electricity when exposed to light. And others to create devices with materials that respond to the environment or influence other reactions.
These are useful examples, the paper says, but much more is possible if we could work with the properties of the very cells, like the bacteria, of which the material that is used is made. Genetic engineering now allows us to control the features of cells, and hence to plan with precision the properties of resulting materials. The team hence undertook creating a bio-ink that is made entirely of genetically engineered bacteria. It has been possible, the paper says, to ensure that the bio-ink is structurally stable and amenable to being cast in specific shapes. And then, to have the objects created by 3-D printing use active material, with ‘therapeutic, sequestering and regulatable’ capabilities.
The qualities that bio-inks need, the paper says, is that they be free-flowing, so that they can laid on to create required shapes, yet sufficiently firm to retain the shape they are given. Bio-inks are thus such material materials, which are compatible with biological material, that can function as a framework to shape the growth of living cells. The team now examined the possibility of constructing this framework itself out of the functional cells that framework was to support.
In earlier, work, the authors say, the team had developed methods to attach bits of proteins to the fibrous exterior of escherichia coli, or e-coli, a common bacterium. To improve the properties of e-coli films, the team turned to components of fibrin – the protein that helps in binding together blood cells to form rigid clots. With the help of genetic engineering, the team created in e-coli a parallel of the ‘knob and hole’ linking mechanism that is found in fibrn. E-coli films then mimicked the binding of fibrin, and could form crosslinks, so that the free-flowing films formed into fibres that were more robust.
Having thus developed a strain of e-coli that could be the material of 3-D printed structures, the team proceeded to enable the e-coli with therapeutic components. First, they programmed e-coli to respond to a specific chemical signal by synthesizing and secreting azurin, a biological anticancer drug. Microbial ink made of these cells was now used to print a 2-D pattern, and the pattern was incubated in two separate media- one which contained the signaling agent, and one which did not. In 24 hours, the medium which had the agent showed the presence of azurin.
Another trial was by grafting e-coli with a bit of protein that formed a bond with bisphenol-A, a toxic chemical. A pattern that was printed with bio-ink that contained these cells was then incubated in a medium that contained bisphenol-A. The pattern was seen to capture 8% of the toxin within 12 hours and 27% in 24 hours, while normal microbial ink did not.
A final trial was to show that e-coli could be programmed to regulate its own rate of growth. E-coli was engineered to produce, when signaled as in the first case, a chemical toxin that arrested cell growth and led to cell death. These cells, in a printed structure, were seen to proliferate in the absence of the signal, but shrank by two orders of magnitude when the signal was present.
What has been done is to create, just by genetic engineering, a stable, 3-D printable material, which can form structures, that can be induced, by a chemical signal, to produce an anti-cancer drug, to sequester a toxin and then to control its own cell growth. There is an “ever-growing toolkit of biological parts being developed by synthetic biologists,” the paper says, and microbial ink can be customized to serve different functions, in medicine and other spheres. There could be applications in the existing use of living cells in building materials. And this could extend to space travel, where we could need to generate materials on demand, with scarce resources, the paper says.
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