Real nanobots !!!! (???)

With fancy chemicals being developed for new medicines, a question remains: how can we deliver the most bang for the buck? It would be ideal to have a microscale delivery truck, capable of delivering the drug to the precise location needed. This would also eliminate many side effects experienced through a general delivery of the drug.

 Catalytic nanoswimmers are being researched as potential cargo vehicles. They are tiny spheres, with one half coated with a reactive material. This side reacts with chemicals in the environment, and the energy of reaction is transmitted into motion forward. Attach a blob of drug to them, and they can move medicine. But questions remain about how to get them to go a specific direction, without having to babysit them. Can we make these trucks driverless?

One way to direct these particles is to establish a fuel concentration gradient. The particles will be ‘attracted’ to the hot spot, though they have no free will.

In a recent paper, researchers say while this approach is interesting, it can’t be the solution. After all, the fuel molecules are not necessarily always the signal you want the swimmers to react to.

They explore another signal: a pH gradient.

Hydrogel particles can swell or shrink in size when the acidity of the environment changes. Particles are  smaller in high acidity, and larger in low acidity. By exposing hydrogel catalytic swimmers to a pH gradient, the team was able to accumulate the swimmers in high pH regions. Cancer cells, as an example, can cause acidity changes.

So why does this accumulation happen? First, the high pH makes the particles larger, which makes their diffusion – the random motions experienced at the microscale – slower. Thus (smaller) particles in low pH regions will be kicked out more often, and settle in the high pH region. The smaller particles also undergo more (random) rotational motion, and this ends up being a double whammy for remaining happy in low pH regions.

I was struck by this paper as it was in nice contrast-and-compare to the run-and-tumble motion of E. Coli. bacteria, as is mentioned in the paper. Both systems are governed by the same physics, at the same scales. E. Coli turns its motor off to tumble and rotate, and figure out where the food is. It then turns the motor back on when it finds somewhere to go.  The catalytic swimmers have no such on/off switch, but can still get to where they need to go.

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How DO bacteria swim with no arms?

You had to skip breakfast today. To compound your misery, a delicious smell
permeates the office. Who ordered pizza? Your stomach growls. You wander around
the hallways and follow your nose to the source of the smell. A few boxes sit unat-
tended in the conference room. A sign in your boss’s handwriting threatens, “DO
NOT EAT.” You sneak a slice anyway, undetected. How do bacteria find food when
they are hungry? It turns out, even though they don’t have noses, they use a simi-
lar tactic. They sense the direction of nutrients by sampling their external chemical
environment, then swim in the appropriate direction. The entire process is called
chemotaxis. While the process of bacterial “smelling” is interesting on its own, the
simple act of swimming is also worth studying.

In a recent issue of the journal Proceedings of the National Academy of Sci-
ences, researchers at the University of Pittsburgh led by Professor Xiao-Lun Wu
reported on the swimming of the bacterium Vibrio alginolyticus and contrasted it to
the swimming of the well-known E. coli bacterium. V. alginolyticus is a species of
marine bacteria. You may be come infected with it if you eat some bad sushi. The
team took high-speed videos of the swimming motions of both bacteria and found
intriguing results.

The swimming of E. coli bacteria has been studied for quite some time, and
the team found nothing surprising there. E. coli bacteria are quite familiar to us as
they live in our lower intestinal tract. Each bacterium has a cigar-shaped head and a
bundle of corkscrew shaped tails called flagella. The bacterium propels itself forward
by turning the corkscrews counterclockwise together. To change direction, some of
the corkscrews start turning clockwise, ending the forward “run.” The bacterium then
rotates or “tumbles” randomly due to external kicks from its environment. During
this tumbling, it “smells” each angle and finds the best direction to run next. If it’s
already near a source of food, the bacterium alternates between these two motions in
a complicated dance to keep itself close.

This run-and-tumble pattern works for E. coli, but cannot work for all forms
of bacteria. Some bacteria, such as V. alginolyticus, are cursed with only one tail.
At face value this may not seem like too much of an impediment. However, due to a
mathematical constraint (the scallop theorem) these bacteria can only propel them-
selves forward or backward, and so cannot enter the neutral tumbling state to change
direction. So singly-corkscrewed bacteria must alternate forward and backward steps
until they happen to be in the right direction they want to be. It’s similar to wiggling
out of a parallel parking space. Since turning is theoretically so inefficient, one would
expect chemotaxis to be a slow process for these bacteria.

But Dr. Wu’s research team found a surprising result when they studied V.
alginolyticus. While the bacterium undergoes run-and-reverse motion as expected, it
also undergoes a previously undiscovered third motion: the flagellum flicks quickly
like a whip, which reorients the bacterium in a random direction in less than 1/20
of a second. This active reorientation is much faster than the passive tumbling of E.
coli. Also, since these bacteria can move backwards (unlike E. coli ) they can precisely
regulate their position more easily: if they overshoot, they can always go back. In
fact, when they compared V. alginolyticus and E. coli head-to-head, V. alginolyti-
cus reached the nutrients about three times faster than E. coli. Additionally, since
they can control their position more carefully, swarms of V. alginolyticus are able to
congregate in much tighter groups (about 7 times as dense) and so maximize their
nutrient dose per organism.

But don’t feel sorry for E. coli. It lives in the relatively utopian environment
of our intestines. Food is plentiful and there are no fast flows disrupting the bacteria
or the nutrients. Contrast this to the native environment of V. alginolyticus. Food is
scarce and harsh ocean currents can wash it away in an instant. The bacteria abso-
lutely must be efficient in order to live. In short, both species seem to have adapted
solutions appropriate to their natural habitat.

The research team does not currently have an explanation for the mechanics
of the novel flicking behavior of V. alginolyticus. However, they do propose that this
could be a widespread feature of marine bacteria due to the previously mentioned
need for efficient scavenging. Finally, while these details of bacterial motion are
interesting from a fundamental research perspective, this work also carries greater
consequences. If we can gain a better comprehension of how bacteria move, we can
possibly come up with new ways to keep them from spreading. Perhaps in the future
we can simply introduce physical obstacles that prevent bacteria from swimming,
as opposed to resorting to antibiotics. And as bacteria can develop a resistance to
antibiotics, humans can easily become desensitized to threatening notes. So, if your
boss really wanted to prevent you from stealing that pizza, a simple locked door would
have been a more suitable countermeasure.