Tag Archives: cells

Hitchhikers at the nanoscale show how cells stir themselves

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A May 30, 2014 news item on Nanowerk highlights some molecule-tracking research,

Chemical engineers from Rice University and biophysicists from Georg-August Universität Göttingen in Germany and the VU University Amsterdam in the Netherlands have successfully tracked single molecules inside living cells with carbon nanotubes.

Through this new method, the researchers found that cells stir their interiors using the same motor proteins that serve in muscle contraction.

A May 29, 2014 Rice University news release by Mike Williams, which originated the news item, describes the researchers’ work,

The team attached carbon nanotubes to transport molecules known as kinesin motors to visualize and track them as they moved through the cytoplasm of living cells.

…

Carbon nanotubes are hollow cylinders of pure carbon with one-atom-thick walls. They naturally fluoresce with near-infrared wavelengths when exposed to visible light, a property discovered at Rice by Professor Rick Smalley a decade ago and then leveraged by Rice Professor Bruce Weisman to image carbon nanotubes. When attached to a molecule, the hitchhiking nanotubes serve as tiny beacons that can be precisely tracked over long periods of time to investigate small, random motions inside cells.

“Any probe that can hitch the length and breadth of the cell, rough it, slum it, struggle against terrible odds, win through and still know where its protein is, is clearly a probe to be reckoned with,” said lead author Nikta Fakhri, paraphrasing “The Hitchhiker’s Guide to the Galaxy.” Fakhri, who earned her Rice doctorate in Pasquali’s lab in 2011, is currently a Human Frontier Science Program Fellow at Göttingen.

“In fact, the exceptional stability of these probes made it possible to observe intracellular motions from times as short as milliseconds to as long as hours,” she said.

For long-distance transport, such as along the long axons of nerve cells, cells usually employ motor proteins tied to lipid vesicles, the cell’s “cargo containers.” This process involves considerable logistics: Cargo needs to be packed, attached to the motors and sent off in the right direction.

“This research has helped uncover an additional, much simpler mechanism for transport within the cell interior,” said principal investigator Christoph Schmidt, a professor of physics at Göttingen. “Cells vigorously stir themselves, much in the way a chemist would accelerate a reaction by shaking a test tube. This will help them to move objects around in the highly crowded cellular environment.”

The researchers showed the same type of motor protein used for muscle contraction is responsible for stirring. They reached this conclusion after exposing the cells to drugs that suppressed these specific motor proteins. The tests showed that the stirring was suppressed as well.

The mechanical cytoskeleton of cells consists of networks of protein filaments, like actin. Within the cell, the motor protein myosin forms bundles that actively contract the actin network for short periods. The researchers found random pinching of the elastic actin network by many myosin bundles resulted in the global internal stirring of the cell. Both actin and myosin play a similar role in muscle contraction.

The highly accurate measurements of internal fluctuations in the cells were explained in a theoretical model developed by VU co-author Fred MacKintosh, who used the elastic properties of the cytoskeleton and the force-generation characteristics of the motors.

“The new discovery not only promotes our understanding of cell dynamics, but also points to interesting possibilities in designing ‘active’ technical materials,” said Fakhri, who will soon join the Massachusetts Institute of Technology faculty as an assistant professor of physics. “Imagine a microscopic biomedical device that mixes tiny samples of blood with reagents to detect disease or smart filters that separate squishy from rigid materials.”

There is an accompanying video,

This video is typical of the kind of visual image that nanoscientists look at and provides an interesting contrast to ‘nano art’ where colours and other enhancements are added. as per this example, NanoOrchard, from a May 13, 2014 news item on Nanowerk about the 2014 Materials Research Society spring meeting and their Science as Art competition,

NanoOrchard – Electrochemically overgrown CuNi nanopillars. (Image courtesy of the Materials Research Society Science as Art Competition and Josep Nogues, Institut Catala de Nanociencia i Nanotecnologia (ICN2), Spain, and A. Varea, E. Pellicer, S. Suriñach, M.D. Baro, J. Sort, Univ. Autonoma de Barcelona) [downloaded from http://www.nanowerk.com/nanotechnology-news/newsid=35631.php]

NanoOrchard – Electrochemically overgrown CuNi nanopillars. (Image courtesy of the Materials Research Society Science as Art Competition and Josep Nogues, Institut Catala de Nanociencia i Nanotecnologia (ICN2), Spain, and A. Varea, E. Pellicer, S. Suriñach, M.D. Baro, J. Sort, Univ. Autonoma de Barcelona) [downloaded from http://www.nanowerk.com/nanotechnology-news/newsid=35631.php]

Getting back to the carbon nanotube hitchhikers, here’s a link to and a citation for the paper,

High-resolution mapping of intracellular fluctuations using carbon nanotubes by Nikta Fakhri, Alok D. Wessel, Charlotte Willms, Matteo Pasquali, Dieter R. Klopfenstein, Frederick C. MacKintosh, and Christoph F. Schmidt. Science 30 May 2014: Vol. 344 no. 6187 pp. 1031-1035 DOI: 10.1126/science.1250170

This article is behind a paywall.

One final comment, I am delighted by the researcher’s reference to the Hitchhiker’s Guide to the Galaxy.

Hands, Waldo, and nano-scalpels

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Hands were featured in Waldo (a 1943 short story by Robert Heinlein) and in Richard Feynman’s “Plenty of room at the bottom” 1959 lecture both of which were concerned with describing a field we now call nanotechnology. As I put it in my Aug. 17, 2009 posting,

Both of these texts feature the development of ‘smaller and smaller robotic hands to manipulate matter at the atomic and molecular levels’ and both of these have been cited as the birth of nanotechnology.

The details are a bit sketchy but it seems that scientists at the University of Bath (UK) have created a tiny (nanoscale) tool that looks like a hand. From the University of Bath’s Dec. 12, 2011 news release,

The lower picture shows the AFM probe with the nano-hand circled. The upper image is a vastly enlarged image of the nano-hand, showing the beckoning motion spotted by Dr Gordeev.

Here’s a little more about Dr. Gordeev’s observation from the Dec. 12, 2011 news item on Nanowerk,

Dr Sergey Gordeev, from the Department of Physics, was trying to create a nano-scalpel, a tool which can be used by biologists to look inside cells, when the process went wrong.

Dr Gordeev said: “I was amazed when I looked at the nano-scalpel and saw what appeared to be a beckoning hand.

“Nanoscience research is moving very fast at the moment, so maybe the nano-hand is trying to attract people and funders into this area.

…

The research group is using funding from Bath Ventures, an organisation which commercialises the results of the University’s research, and private company Diamond Hard Surfaces Ltd, to explore the use of hard coatings for nano-tools, making them more durable and suitable for delicate biological procedures.

I appreciate Dr. Gordeev’s whimsical notion that the hand might be trying to attract funding for this research group.

Cells and transistors

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Analog/digital, is there a difference? After reading the latest from MIT’s (Massachusetts Institute of Technology) Research Laboratory Electronics (RLE), the answer turns out to be no, when it comes to transistors. From the Sept. 29, 2011 news item on Nanowerk,

A transistor is basically a switch: When it’s on, it conducts electricity; when it’s off, it doesn’t. [emphases mine] In a computer chip, those two states represent 0s and 1s.

But in moving between its nonconductive and conductive states, a transistor passes through every state in between — slightly conductive, moderately conductive, fairly conductive — just as a car accelerating from zero to 60 passes through every speed in between. Because the transistors in a computer chip are intended to perform binary logic operations, they’re designed to make those transitional states undetectable. [emphases mine]

The MIT researchers will be discussing their work using analog transistors to increase the concentrations of two different proteins in cells. From the news item on Nanowerk,

At the Biomedical Circuits and Systems Conference in San Diego in November, Sarpeshkar [Rahul Sarpeshkar, associate professor of electrical engineering], research scientist Lorenzo Turicchia, postdoc Ramiz Daniel and graduate student Sung Sik Woo, all of RLE, will present a paper in which they use analog electronic circuits to model two different types of interactions between proteins and DNA in the cell. The circuits mimic the behaviors of the cell with remarkable accuracy, but perhaps more important, they do it with far fewer transistors than a digital model would require.

Here’s a graphic representation of transistors in a cell (downloaded from the MIT News Office page for this research,

Graphic: Christine Daniloff

This works seems to be signaling (pun noted) a change in how systems biology and synthetic biology researchers think about biological systems. From the Sept. 28, 2011 news item by Larry Hardesty for the MIT News Office,

Since the completion of the Human Genome Project, two thriving new disciplines — synthetic biology and systems biology — have emerged from the observation that in some ways, the sequences of chemical reactions that lead to protein production in cells are a lot like electronic circuits. In general, researchers in both fields tend to analyze reactions in terms of binary oppositions: If a chemical is present, one thing happens; if the chemical is absent, a different thing happens.

But Rahul Sarpeshkar, an associate professor of electrical engineering in MIT’s Research Laboratory of Electronics (RLE), thinks that’s the wrong approach. “The signals in cells are not ones or zeroes,” Sarpeshkar says. “That’s an overly simplified abstraction that is kind of a first, crude, useful approximation for what cells do. But everybody knows that’s really wrong.”

From what I understand of the synthetic biology and systems biology communities, this is a major change.