Artificial Cell Components and Membranes, the Start of a Fusion Between Biology and Biotechnology Inside the Body

There will be no bright dividing line between evolved cellular component and artificial molecular machinery in the future of medicine and human enhancement. It is already possible to produce programmable DNA machinery that can react to the environment in simple ways, or to adjust the programming of cells by altering the production or activities of specific proteins. As understanding of the cell improves, it will be possible to produce nanoscale structures that act in similar ways to cellular components. Researchers are starting down this road with the production of various forms of manufactory, artificial membranes that enclose anything from cells or bacteria to a minimal set of DNA or other molecular machinery that can produce specific proteins or other molecules in response to circumstances. The articles below look at the two ends of this scale: an entire cell wrapped in a membrane on the one hand, versus much smaller components designed to be taken up and used by cells, releasing molecules in response to internal signals.

For the future, it is possible to envisage all sorts of further possibilities. Tweaks to existing structures to make them better: enhanced lysosomes equipped with a better range of digestive enzymes, improving the ability of long-lived cells to break down unwanted molecular waste; mitochondria with a stripped down, best of breed mitochondrial genome, based on the most performant of those evolved in our species; protein production and protein clearance structures based upon those found in other species that are much more efficient than the human model; cultured gut bacteria that are designed from the ground up, with minimal genomes, to be entirely beneficial; and more. Or simple artificial cells that replace or augment some of the simpler functions of evolved cells, such as the production of a needed protein or removal of an unwanted protein. Or wholly new structures within a cell that trickle out signal molecules that permanently increase cellular stress responses. Or sophisticated manufactories capable of producing all of the known cancer suppression genes, delivered by the billion, taken up into all cells, where they lie dormant, waiting to triggered into activity in cancerous cells. There are so very many options for improvement.

Further down the line, machinery that looks very different from cells will start to become a viable proposition. Diamondoid nanotechnology, for example, coupled with molecular manufacturing to mass produce devices that look nothing like cells, but can be vastly more efficient than any cell at a specific task. Nanomachines that can store hundreds as times as much oxygen as a red blood cell; that can identify and destroy pathogens without flagging; that can assist in the repair and maintenance of the inner machinery of living cells. The fusion of machine and biology will become highly sophisticated and varied. The importance of the designation of biological or artificial will fade, and ultimately we will become just as designed and enhanced as any of of the countless component parts in our cells.

Artificial and biological cells work together as mini chemical factories

Researchers have fused living and non-living cells for the first time in a way that allows them to work together, paving the way for new applications. The system encapsulates biological cells within an artificial cell. Using this, researchers can harness the natural ability of biological cells to process chemicals while protecting them from the environment. This system could lead to applications such as cellular 'batteries' powered by photosynthesis, synthesis of drugs inside the body, and biological sensors that can withstand harsh conditions.

Previous artificial cell design has involved taking parts of biological cell 'machinery' - such as enzymes that support chemical reactions - and putting them into artificial casings. The new study goes one step further and encapsulates entire cells in artificial casings. The artificial cells also contain enzymes that work in concert with the biological cell to produce new chemicals. In the proof-of-concept experiment, the artificial cell systems produced a fluorescent chemical that allowed the researchers to confirm all was working as expected.

"Biological cells can perform extremely complex functions, but can be difficult to control when trying to harness one aspect. Artificial cells can be programmed more easily but we cannot yet build in much complexity. Our new system bridges the gap between these two approaches by fusing whole biological cells with artificial ones, so that the machinery of both works in concert to produce what we need. This is a paradigm shift in thinking about the way we design artificial cells, which will help accelerate research on applications in healthcare and beyond."

Tiny implants for cells are functional in vivo

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. Researchers are working to produce organelles of this kind in the laboratory, to introduce them into cells, and to control their activity in response to the presence of external factors (e.g. change in pH values or reductive conditions). These cellular implants could, for example, carry enzymes able to convert a pharmaceutical ingredient into the active substance and release it "on demand" under specific conditions. Administering drugs in this way could considerably reduce both the amounts used and the side effects. It would allow treatment to be delivered only when required by changes associated with pathological conditions (e.g., a tumor).

Now, researchers have succeeded in integrating artificial organelles into the cells of living zebrafish embryos. The artificial organelles are based on tiny capsules that form spontaneously in solution from polymers and can enclose various macromolecules such as enzymes. The artificial organelles presented here contained a peroxidase enzyme that only begins to act when specific molecules penetrate the wall of the capsules and support the enzymatic reaction. To control the passage of substances, the researchers incorporated chemically modified natural membrane proteins into the wall of the capsules. These act as gates that open according to the glutathione concentration in the cell. At a low glutathione value, the pore of the membrane proteins are "closed" - that is, no substances can pass. If the glutathione concentration rises above a certain threshold, the protein gate opens and substances from outside can pass through the pore into the cavity of the capsule. There, they are converted by the enzyme inside and the product of the reaction can leave the capsule through the open gate.

The researchers chose zebrafish embryos because their transparent bodies allow excellent tracking of the cellular implants under a microscope when they are marked with a fluorescent dye. After the artificial organelles were injected, they were "eaten" by macrophages and therefore made their way into the organism. The researchers were then able to show that the peroxidase enzyme trapped inside the artificial organelle was activated when hydrogen peroxide produced by the macrophages entered through the protein gates.

Comments

Your growing expertise, from editing this blog, is reflected in the awesome quality of your intro comments (the white part of articles). Bravo!

Posted by: Tom Schaefer at March 21st, 2018 9:18 AM

Interesting, you could "tattoo" someones skin, but instead of using a dye use these synthetic organelles to produce insulin and the protein receptors necessary for the organelle to sense blood sugar from inside the macrophages that ingest them. In Type 1 diabetes the insulin protein subunits would cause immune cells to attack the macrophages just as they attack and kill off the pancreas Beta cells, but in this case you could also get the organelles to produce PD1 ligand proteins, borrowing a trick from cancer cells to turn the immune attack off.

Hopefully someone will get a grant to test something like this on diabetic dogs at some point. It could be a lot easier than attempting an in vivo gene therapy.

Posted by: Jim at March 21st, 2018 10:10 AM

Actually PD1-L is probably not the best idea as it was recently discovered that cancer cells at least export these through exosomes, causing an area of local immune privilage for the entire cancer. Maby some modified form that cannot escape the macrophages?

Posted by: Jim at March 21st, 2018 10:15 AM

Is it just me or is this another Kurzweilian moment?

Every so often I write him off then something like this happens.

Posted by: Mark Borbely at March 21st, 2018 10:47 AM

Mark B, specifically Eric Drexler, but yea, generally Ray K.

Posted by: Robert at March 21st, 2018 12:44 PM

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