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The design of the multi-trap nanophysiometer (MTN) is seen on the left, with a cad rendering on the top right and the actual manufactured device on the bottom right. The MTN allows an unprecedented look at how cell signaling works.  (Source: Vanderbilt)

An artist's rendering of the completed MTN shows cells trapped inside as signals travel to them.  (Source: Vanderbilt)

A photo shows cells trapped in the MTN. The dark gray areas are the trap and the circle inside is a trapped cell. The inset picture shows a fluorescent indicator to cells reacting to a paracrine message. This shows that cells downstream are being signaled.  (Source: Vanderbilt)
A new sensor allows an unprecedented look at cell signaling and may save lives one day

Scientists have developed nanomachines which have targeted cancer cells delivering deadly poisons to kill them, without harming healthy cells.  However, the key to nanodrugs is not merely their creation, but their targeting. 

Just like a missile needs a guidance system to make properly score a hit on its target, the drugs of the future will need means of detecting their enemies.  New breakthroughs in the field of paracrine signaling may soon make such targeting possible.

In the body, cells have multiple ways of signaling.  Some cells send signals to adjacent cells -- this method is very detectable and is well documented.  Sometimes cells send long distance chemical messengers in the blood stream, such as adrenaline.  These signals are also readily detectable.  However, a great deal of the body's signaling is thought to occur at short distances between non-connected cells, known as paracrine signaling.  Paracrine signaling is one of the least understood fields of physiology and just recently have scientists begun to recognize its significance.

The discovery of paracrine signaling, which is detailed in the journal Lab On A Chip.  The MTN was revolutionary in that it could detect minute quantities of paracrine chemicals, previously too dilute to be detected.  Now the researchers have developed a more advanced sensor which pumps cells into the MTN sensor, which traps and cultures them.  The new sensor monitors the trapped cells with a variety of digital and chemical methods to better understand paracrine signaling.

The new device was developed by a research team at the Vanderbilt Institute for Integrative Biosystems Research and Education headed by John P. Wikswo, the Gordon A. Cain University Professor at Vanderbilt.  The device has already provided a never-before-seen glimpse at how dendritic cells (a type of white blood cell) in the immune system signal T-Cells (another type of white blood cell) to destroy infection.

Co-author Derya Unutmaz, now an associate professor of microbiology at New York University's School of Medicine stated, "This is an important advance and potentially very useful technology.  The ability to study the behavior of single cells may not be as critical if you are studying the heart or muscles, which are mostly formed by uniform cells, but it is crucial for understanding how the immune system functions. The wide surveillance of the body that it conducts requires extensive communication between dozens of different kinds of immune cells."

Generally the immune system has stored T Cells in the lymph nodes.  When a dendritic cells sense an invader -- such as the Flu virus, a cancer cell, or the AIDS virus -- it signals T Cells to make preparations to the fight the intruder.  As only a certain percentage of T Cells are tuned to fight each type of intruder, the dendritic cells must properly recruit the right candidates for the job out of millions of cells, a daunting process that previously was a mystery.

Using plastic microfluid channels smaller than a human hair, cells and culture media is pumped into the nanodevice, molded into the bottom of a glass microscope cover slip.  In a special chamber cells are caught in special wells.  Fluid flows out holes in the bottoms of the wells, passively trapping the cells.  Thanks to the media they can be kept alive 24 hours or more, longer than normal.

A digital camera monitors the cells, snapping pictures every 30 seconds.  Software analyzes the cells actions.  In the presence of certain activity indicators such as calcium, phosphorescent dye lights up brightly. 

Graduate student Shannon Faley, now a postdoctoral research associate at the University of Glasgow, Scotland was the first to notice paracrine signaling occurring.  She used an MTN with trapped dendritic cells.  She noticed that the mature dendritic cells signaled some naive T cells that they were in contact with.  However, they also somehow signaled the correct T Cells downstream as well.  She described, "My reaction when I saw them was, 'What in the world is going on?'"

Professor Wikswo further added, "When she saw this, Shannon did a very clever thing.  She took one chamber and filled it with dendritic cells and took a second chamber and filled it with T-cells. Then she hooked the second chamber downstream of the first."

The cells in the second chamber reacted, indicating undeniable presence of a chemical agent.  While researchers still have not identified the precise chemical agent, or what its exact function is, they hope to soon find that out.

The researchers plan to look at paracrine responses to tumor cells, AIDS, and many other deadly diseases.  Based on studying how the immune system works and what "goes wrong" in severe cases like AIDS, better defenses can be developed.  Signaling between cancer cells can also be isolated and be used to target them.  Dana Marshall, associate professor at the Meharry Medical College, and Professor Wikswo have already submitted a proposal to use the device to study triple-negative breast tumors, one of the most deadly forms of breast cancer.

Some cancers such as the aforementioned one respond to chemotherapy for a time and then become immune.  Dr. Marshall stated, "Often, when therapy fails, the tumor responds to a chemotherapy treatment for a period of time and then it stops. This approach may let us figure out why that happens."

The research was funded by grants from the Defense Advanced Research Projects Agency, Air Force Office of Scientific Research, the National Institutes of Health, the Vanderbilt Institute for Integrative Biosystems Research and Education and the Systems Biology and Bioengineering Undergraduate Research Experience.



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AWE-SOME
By therealnickdanger on 9/4/2008 2:05:54 PM , Rating: 2
I like this article, very interesting! The human body is such a remarkable machine, I hope we never figure it all out, there's so much to learn!

(spelling nazi: "previously to dilute to be detected")




RE: AWE-SOME
By whiskerwill on 9/4/2008 2:07:30 PM , Rating: 3
Why do you hope we'll never figure it out? If we did, we could solve disease, aging, everything.


RE: AWE-SOME
By amanojaku on 9/4/2008 2:12:24 PM , Rating: 2
Because we would genetically engineer people with lasers on their heads. Dating would be VERY difficult if the girl doesn't like you.


RE: AWE-SOME
By 5c8wc4 on 9/4/2008 2:24:59 PM , Rating: 2
Not if they alter the girl to like him ;)


RE: AWE-SOME
By Samus on 9/5/2008 4:24:34 AM , Rating: 2
quote:
Not if they alter the girl to like him ;)


this is great technology, but the concept can go to far. when you start altering people against their will (like we already do in the military) we become less and less human.


RE: AWE-SOME
By arazok on 9/4/2008 2:59:07 PM , Rating: 5
Obviously we’d engineer ‘no’ out of their vocabulary. Just like they did in the old days - minus the bruising.


RE: AWE-SOME
By tastyratz on 9/4/2008 3:18:28 PM , Rating: 1
We would genetically engineer them to not be capable of having headaches either. Running out of excuses the fascist rule of the ice queens will crumble!


RE: AWE-SOME
By amanojaku on 9/4/2008 5:22:40 PM , Rating: 2
Be careful. Next thing you know you'll WANT to talk with your girlfriend and not play video games.

"Honey, let's go shopping!"
"Yeaaaaaaaaaaaaaa! Hey, wait a minute!"


RE: AWE-SOME
By Smartless on 9/4/2008 7:32:22 PM , Rating: 2
Wait why am I putting the toilet seat back down. DAMN THEY GOT ME!


RE: AWE-SOME
By Chudilo on 9/5/2008 9:54:50 AM , Rating: 2
I think it would be easier to engineer a toilet seat to know who's approaching it!


RE: AWE-SOME
By Newspapercrane on 9/5/2008 10:26:20 AM , Rating: 2
In the mens room at my girlfriend's dorm the dang toilet seat won't even stay up... I can't figure out if it's broken, or if it's just clever design.


RE: AWE-SOME
By therealnickdanger on 9/4/2008 6:42:52 PM , Rating: 2
Because the unknown spurs innovation and invention.


RE: AWE-SOME
By 67STANG on 9/5/2008 1:54:05 AM , Rating: 2
Nonsense. I hope they find out everything. That way, when I'm 60, they can fix my liver and my lungs.


RE: AWE-SOME
By therealnickdanger on 9/5/2008 1:43:44 PM , Rating: 2
That is either the funniest comment I've read or the saddest.


Cell comunication
By oTAL on 9/4/2008 2:37:53 PM , Rating: 2
quote:
The cells in the second chamber reacted, indicating undeniable presence of a chemical agent.


Undeniable, uh? Have they found a chemical?? No? well then...
It could be God telling them what to do... or *gasp* the Devil!!

My feeling is that it has something to do with medichlorians.

All joking aside, there is the slight possibility that these cells can communicate by non-chemical means (I don't mean the Force, I mean electrical impulses, magnetic changes, vibrations, whatever).




RE: Cell comunication
By shin0bi272 on 9/4/2008 3:28:02 PM , Rating: 2
Well ICF (inter cellular fluid) is mostly water so it could be electrical or chemical. But I think the bigger question here is when will we have nanites or nanoprobes or whatever you want to call them swimming around in our bodies keeping us healthy?


RE: Cell comunication
By StevoLincolnite on 9/5/2008 12:33:28 AM , Rating: 2
I have such a bad thing against Nanites in the human body, You just need someone to make them Replicate, and Program to take control of you and you are officially FUBAR! (I watch to much Stargate, Anyway AFK).


RE: Cell comunication
By G2cool on 9/5/2008 9:39:11 AM , Rating: 2
Resistance is futile


RE: Cell comunication
By TimberJon on 9/4/2008 4:15:43 PM , Rating: 1
How marvelously are our bodies made. We will really be in shock if there are no chemical or electrical signals. If there is no evidence of anything keeping them in communication, then that's just trippy, but enforces that God's Will keeps order in the universe and keeps it bound together every millisecond and all that.

Personally, I hope that there is some trigger involved that we can detect and/or measure. If there is great!, but then I wouldnt put it past God to build in a few redundancies either. We do it with imperfect machinery... Why wouldnt he build it into a perfect being in the beginning?

We are technically like Yuuzahn Vong, we've been stripped of immortality.


RE: Cell comunication
By StevoLincolnite on 9/5/2008 12:38:34 AM , Rating: 2
Human's are a "Perfect Being?" - Since when? We kill each other, sometimes for fun or possession of items, Some human beings are complete whacko's... And Who in there right mind would create women to Have "Monthlies" Which is a horrible time for any Female... OR MALE!

Seriously, If we were Perfect, I doubt anyone on this planet would be over-weight, Disabilities, Mental Illnesses and what not, and we would probably all look like as if we belong on Baywatch, Seriously, If we were Perfect why would God give us the ability to Fart? It's Putrid (unless it's your own).


RE: Cell comunication
By foolsgambit11 on 9/5/2008 1:12:32 PM , Rating: 2
You don't build in redundancy if the system is perfect. The point of redundancy is to have a backup if the primary system breaks. If the primary system is perfect, it won't break. Then the redundant system becomes extraneous - therefore imperfect.

Of course, you could mean perfect only in the sense that human beings are exactly what He intended to make - perfectly executed, rather than perfectly designed. But who are we to assume we know the plans of God?

In other words, your comments don't fit in well on a science and technology site, because they fail the empiricism test. That's probably why you were rated down.


I like this stuff.
By Mitch101 on 9/4/2008 2:31:17 PM , Rating: 1
Makes you wonder if they can channel cells like this why not gate them and if an irregular cell is in the channel hit it with a laser or channel it out of the body.

Kind of like a microscopic security checkpoint cleaning out the bad cells.




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