Protected: 2 kinds of mole rats, 2 different cancer-fighting techniques

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Protein Folding

I’m currently in the process of going through a monstrous stack of periodicals I’ve accumulated, including the magazine Physics Today, which comes with my APS membership.

This article by Ashley Smart is simply a research summary on experiments on proteins.

But Smart evoked a lot of thoughts about proteins. We need them to be folded correctly to work, but how are they folded? How is this the minimum energy state.

Smart’s description of various denatured (unfolded) proteins reminded me a lot of the language used in the glass/jamming community. A fried egg consists of proteins denatured by heat. A similar transition happens for
“glassy” systems: raise the temperature and the material will flow.

Mechanical stress can cause also cause the protein in egg white to denature, resulting in a foamy, stiff, meringue. In jammed systems, like mayonnaise, mechanical stress (i.e. using a butter knife) causes the material to unjam (i.e. deform and spread on the sandwich).

The third variable discussed in the jamming community is volume fraction, which I won’t delve into here. The third variable for the egg example is acidity, mixing egg whites with lime juice will also cause the proteins to denature. Completely different, can’t win ’em all.

What also drew me into this simple piece was the description of the experiments. (Smart does a commendable job of trying to explain the math in words.) There are two processes that contribute to the overall signal the researchers measure, only one of which relates to protein folding. But if you change the temperature, each process responds on a vastly different timescale.Taking measurements at the right frequency and using a trick of derivatives, they can isolate the process of interest. An experiment like this would be a great lab in a biophysics class.

Naked Mole Rats FTW

I have seriously been told I resemble a naked mole rat when I’m roused from sweet, sweet slumber. My eyes refuse to open, and I burrow under the sheets. I’m pretty pale and mostly hairless, too.

While I hope I don’t resemble a naked mole rat in all ways (a bit on the uncomely side) I think there’s reason to hope my cells act like their’s.

Naked mole rats never get cancer.

It appears they don’t get cancer because their cells experience “contact inhibition.”

Humans get cancer quite a bit, and the odds increase as we age. The chances of a cell switching to cancerous increase, simply because we’ve given them more chances to do so. Lab mice get cancer about 70% of the time, if allowed to live for several years.

Human and mouse cells experience this contact inhibition phenomenon as well. Cells divide and fill up the space they’re in. Once they touch, they generally slow down their division; there are enough cells.

Cancer cells don’t have this contact inhibition, and grow wildly, unchecked.

Naked mole rat cells, when studied in the lab, exhibit a super kind of contact inhibition – cell division completely stops when cells touch.

In the future, perhaps we can identify what causes this, and turn on a switch in our own bodies if we suspect we have cancer.

 

Adhesion, Geckos, and Technology

One of our earlier experiences with science comes in kindergarten. The teacher brings out the Elmer’s glue and we put macaroni on construction paper. The white viscous stuff acts to permanently bond the paper and pasta. As children we’re ignorant of the science beneath this and view glue as magic stuff. But if we could zoom in to resolve the detail, we’d see the long squiggly polymer molecules in the glue are grabbing onto the fibers in the paper as well as the starch fibers in the macaroni. The glue acts as an adhesive.

Adhesion refers to whether or not two different surfaces stick together. [Aside: cohesion refers to how molecules within a substance are attracted to one another, one might think of it as ‘self-stickiness.’] In our glue example, there are actually two interfaces of adhesion, the glue/paper and the glue/macaroni. There are different varieties of adhesion. There is chemical adhesion, which involves actually forming a new bond between the molecules of each surface. There is the physical, grabbing adhesion of glue mentioned before. There is adhesion due to electric charge. That static cling sticker dedicated to your alma mater on your car window uses this kind of adhesion. There is even yet another type of adhesion. Even if there is no chemical bond, polymer grabbing, or charge attracting two surfaces, there is still likely to be a force of adhesion called “van der Waals” adhesion. The precise details of van der Waals adhesion will not be explored here, but it is the same van der Waals interaction (sometimes referred to as ‘London dispersion force’) many learn about in high school chemistry. Van der Waals adhesion can be surprisingly strong, as we will see.

Geckos are quite amazing in their ability to perform seemingly impossible feats of climbing. They can even easily climb up and down a smooth glass aquarium cage, a surface with no obvious footholds! Yet if you hold a gecko in your hand their feet don’t feel especially sticky. Each of their toe pads is covered with about 100,000 setae, basically short hairs. The setae then split into hundreds of tips, each about 200 nanometers in diameter. These setae tips are what touch the glass, so there must be some type of adhesion between the tips and the surface to support the gecko’s weight. Autumn and coworkers [1] cleverly demonstrated the exact nature of this adhesion. Since they produce no glue, chemical and physical mechanisms were not on the table. However, there were two dry adhesion candidates: charged and van der Waals. The team let the geckos crawl up and down smooth surfaces that were charged differently. They performed equally well on both surfaces, pointing to van der Waals adhesion as the culprit.

However, since this adhesion is strong enough to keep the gecko firmly affixed to a wall, then how do they unstick? Geckos can crawl quite quickly, so there must be an unsticking mechanism in place. The same group came forth [2] to answer this question. With a series of experiments (including forcing a gecko to hang by one toe) the team showed that the setae tips are angled. This has the net effect of increasing the adhesion forces when at they are on surfaces at steeper angle: the setae tips become stickier as needed! Further, the angled attachment affords easy detachment: there is essentially no force required to move the foot up. They also have a “reverse gear” in their back feet for moving down surfaces, where the tips are oriented in the opposite direction.

Recently, Suh and coworkers [3] have been trying to recreate this remarkable gecko adhesion synthetically. After all, this adhesion has many desirable qualities. It’s strong, yet completely reversible. It can adhere to various degrees of surface roughness and any surface orientation. These qualities are especially suited to precise tasks such as moving and manipulating sensitive electronic components. The group was able to fabricate 200 nanometer plastic ‘hairs’ on a flat surface, resembling the setae tips of the gecko. These hairs were angled as well, and a 1 inch patch of them was capable of transporting a piece of glass that was 300 times that large! However, this system relies on needing to hit the hairs at the correct angle, and so is really a passive adhesion mechanism. While the gecko uses the same basic mechanism, it is actively controlling the contact with its muscles. Unfortunately, the synthetic version would not be suited to any complex task.

So while originally inspired by the gecko, the group ultimately developed a better system for practical use [4]. They stretched out a thick sheet of rubber and treated it with a reactive gas, so only the top surface was modified and became stiffer. When the sheet was allowed to relax, it went back to its original size. However, the top surface was no longer happy in this state, and created a wrinkly pattern on the surface, like a shallow egg crate. They then stretched it again, and put small (1/50th of a millimeter) pillars on the surface. So, when the sheet is relaxed, the pillars do not stick straight up, rather they are at odd angles due to the wrinkling, and when stretched they stick straight up. This creates a simple on/off adhesion mechanism. In the stretched state, the top of every pillar can make good contact with another surface, and in the relaxed state, none of the pillars can. They were able to pick up and move the same piece of glass in a complex choreography, all without leaving the even the slightest trace on the surface.

[1] Autumn, K. et al. PNAS 99, 12252 (2002)

[2] Autumn, K. et al. Journal of Experimental Biology 209, 3569 (2006)

[3] Suh, K.Y. et al. PNAS 106, 5639 (2009)

[4] Suh, K.Y. et al. Langmuir 26, 2223 (2010)

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.