Last year, a team of biologists and computer scientists from Tufts University and the University
of Vermont (UVM) created novel, tiny self-healing biological machines from frog cells called
“Xenobots” that could move around, push a payload, and even exhibit collective behavior
in the presence of a swarm of other Xenobots.
The same team has now created life forms that self-assemble a body from single cells, do
not require muscle cells to move, and even demonstrate the capability of recordable memory.
The new generation Xenobots also move faster, navigate different environments, and have
longer lifespans than the first edition, and they still have the ability to work together
in groups and heal themselves if damaged.
The results of the new research were published in the journal Science Robotics.
Compared to Xenobots 1.0, in which the millimeter-sized automatons were constructed in a “top down”
approach by manual placement of tissue and surgical shaping of frog skin and cardiac
cells to produce motion, the next version of Xenobots takes a “bottom up” approach.
The biologists at Tufts took stem cells from embryos of the African frog Xenopus laevis
and allowed them to self-assemble and grow into spheroids, where some of the cells after
a few days differentiated to produce cilia – tiny hair-like projections that move back
and forth or rotate in a specific way.
Instead of using manually sculpted cardiac cells whose natural rhythmic contractions
allowed the original Xenobots to scuttle around, cilia give the new spheroidal bots “legs”
to move them rapidly across a surface.
In a frog, or human for that matter, cilia would normally be found on mucous surfaces,
like in the lungs, to help push out pathogens and other foreign material.
On the Xenobots, they are repurposed to provide rapid locomotion.
In a way, the Xenobots are constructed much like a traditional robot.
Only the researchers use cells and tissues rather than artificial components to build
the shape and create predictable behavior.
On the biology end, this approach is helping the researchers understand how cells communicate
as they interact with one another during development, and how they might better control those interactions.
While the Tufts scientists created the physical organisms, scientists at UVM were busy running
computer simulations that modeled different shapes of the Xenobots to see if they might
exhibit different behaviors, both individually and in groups.
Using the Deep Green supercomputer cluster at UVM's Vermont Advanced Computing Core,
the team simulated the Xenbots under hundreds of thousands of random environmental conditions
using an evolutionary algorithm.
These simulations were used to identify Xenobots most able to work together in swarms to gather
large piles of debris in a field of particles.
The researchers say that they want Xenobots to do useful work.
Right now they are giving them simple tasks, but ultimately they are aiming for a new kind
of living tool that could, for example, clean up microplastics in the ocean or contaminants
in soil.
It turns out, the new Xenobots are much faster and better at tasks such as garbage collection
than last year’s model, working together in a swarm to sweep through a petri dish and
gather larger piles of iron oxide particles.
They can also cover large flat surfaces, or travel through narrow capillaries.
These studies also suggest that the in silico simulations could in the future optimize additional
features of biological bots for more complex behaviors.
One important feature added in the Xenobot upgrade is the ability to record information.
A central feature of robotics is the ability to record memory and use that information
to modify the robot’s actions and behavior.
With that in mind, the Tufts scientists engineered the Xenobots with a read/write capability
to record one bit of information, using a fluorescent reporter protein called EosFP,
which normally glows green.
However, when exposed to light at 390nm wavelength, the protein emits red light instead.
The cells of the frog embryos were injected with messenger RNA coding for the EosFP protein
before stem cells were excised to create the Xenobots.
The mature Xenobots now have a built-in fluorescent switch which can record exposure to blue light
around 390nm.
The researchers tested the memory function by allowing 10 Xenobots to swim around a surface
on which one spot is illuminated with a beam of 390nm light.
After two hours, they found that three bots emitted red light.
The rest remained their original green, effectively recording the “travel experience” of the
bots.
This proof of principle of molecular memory could be extended in the future to detect
and record not only light but also the presence of radioactive contamination, chemical pollutants,
drugs, or a disease condition.
Further engineering of the memory function could enable the recording of multiple stimuli
(more bits of information) or allow the bots to release compounds or change behavior upon
sensation of stimuli.
One thing the Xenobots and future versions of biological bots can do that their metal
and plastic counterparts have difficulty doing is constructing their own body plan as the
cells grow and mature, and then repairing and restoring themselves if they become damaged.
Healing is a natural feature of living organisms, and it is preserved in Xenobot biology.
The new Xenobots were remarkably adept at healing and would close the majority of a
severe full-length laceration half their thickness within 5 minutes of the injury.
All injured bots were able to ultimately heal the wound, restore their shape and continue
their work as before.
Another advantage of a biological robot is metabolism.
Unlike metal and plastic robots, the cells in a biological robot can absorb and break
down chemicals and work like tiny factories synthesizing and excreting chemicals and proteins.
The whole field of synthetic biology – which has largely focused on reprogramming single
celled organisms to produce useful molecules - can now be exploited in these multicellular
creatures.
Like the original Xenobots, the upgraded bots can survive up to ten days on their embryonic
energy stores and run their tasks without additional energy sources, but they can also
carry on at full speed for many months if kept in a “soup” of nutrients.
Xenobots and their successors may also provide insight into how multicellular organisms arose
from ancient single celled organisms, and the origins of information processing, decision
making and cognition in biological organisms.
Recognizing the tremendous future for this technology, Tufts University and the University
of Vermont have established the Institute for Computer Designed Organisms (ICDO), to
be formally launched in the coming months, which will pull together resources from each
university and outside sources to create living robots with increasingly sophisticated capabilities.
The ultimate goal for the Tufts and UVM researchers is not only to explore the full scope of biological
robots they can make; it is also to understand the relationship between the ‘hardware’
of the genome and the ‘software’ of cellular communications that go into creating organized
tissues, organs and limbs.
Then we can gain greater control of that morphogenesis for regenerative medicine, and the treatment
of cancer and diseases of aging.