Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Putting the Squeeze on Cells

Published: Wednesday, January 23, 2013
Last Updated: Wednesday, January 23, 2013
Bookmark and Share
By deforming cells, researchers can deliver RNA, proteins and nanoparticles for many applications.

Living cells are surrounded by a membrane that tightly regulates what gets in and out of the cell. This barrier is necessary for cells to control their internal environment, but it makes it more difficult for scientists to deliver large molecules such as nanoparticles for imaging, or proteins that can reprogram them into pluripotent stem cells.

Researchers from MIT have now found a safe and efficient way to get large molecules through the cell membrane, by squeezing the cells through a narrow constriction that opens up tiny, temporary holes in the membrane. Any large molecules floating outside the cell — such as RNA, proteins or nanoparticles — can slide through the membrane during this disruption.

Using this technique, the researchers were able to deliver reprogramming proteins and generate induced pluripotent stem cells with a success rate 10 to 100 times better than any existing method. They also used it to deliver nanoparticles, including carbon nanotubes and quantum dots, which can be used to image cells and monitor what’s happening inside them.

“It’s very useful to be able to get large molecules into cells. We thought it might be interesting if you could have a relatively simple system that could deliver many different compounds,” says Klavs Jensen, the Warren K. Lewis Professor of Chemical Engineering, professor of materials science and engineering, and a senior author of a paper describing the new device in this week’s issue of the Proceedings of the National Academy of Sciences.

Robert Langer, the David H. Koch Institute Professor at MIT, is also a senior author of the paper. Lead authors are chemical engineering graduate student Armon Sharei, Koch Institute research scientist Janet Zoldan, and chemical engineering research associate Andrea Adamo.

A general approach

Biologists have previously developed several ways to get large molecules into cells, but all of them have drawbacks. DNA or RNA can be packaged into viruses, which are adept at entering cells, but that approach carries the risk that some of the viral DNA will get integrated into the host cell. This method is commonly used in lab experiments but has not been approved by the FDA for use in human patients.

Another way to sneak large molecules into a cell is to tag them with a short protein that can penetrate the cell membrane and drag the larger cargo along with it. Alternatively, DNA or proteins can be packaged into synthetic nanoparticles that can enter cells. However, these systems often need to be re-engineered depending on the type of cell and material being delivered. Also, with some nanoparticles much of the material ends up trapped in protective sacs called endosomes inside the cell, and there can be potential toxic side effects.

Electroporation, which involves giving cells a jolt of electricity that opens up the cell membrane, is a more general approach but can be damaging to both cells and the material being delivered.

The new MIT system appears to work for many cell types — so far, the researchers have successfully tested it with more than a dozen types, including both human and mouse cells. It also works in cells taken directly from human patients, which are usually much more difficult to manipulate than human cell lines grown specifically for lab research.

The new device builds on previous work by Jensen and Langer’s labs, in which they used microinjection to force large molecules into cells as they flowed through a microfluidic device. This wasn’t as fast as the researchers would have liked, but during these studies, they discovered that when a cell is squeezed through a narrow tube, small holes open in the cell membrane, allowing nearby molecules to diffuse into the cell.

To take advantage of that, the researchers built rectangular microfluidic chips, about the size of a quarter, with 40 to 70 parallel channels. Cells are suspended in a solution with the material to be delivered and flowed through the channel at high speed — about one meter per second. Halfway through the channel, the cells pass through a constriction about 30 to 80 percent smaller than the cells’ diameter. The cells don’t suffer any irreparable damage, and they maintain their normal functions after the treatment.

Special delivery

The research team is now further pursuing stem cell manipulation, which holds promise for treating a wide range of diseases. They have already shown that they can transform human fibroblast cells into pluripotent stem cells, and now plan to start working on delivering the proteins needed to differentiate stem cells into specialized tissues.

Another promising application is delivering quantum dots — nanoparticles made of semiconducting metals that fluoresce. These dots hold promise for labeling individual proteins or other molecules inside cells, but scientists have had trouble getting them through the cell membrane without getting trapped in endosomes.

In a paper published in November, working with MIT graduate student Jungmin Lee and chemistry professor Moungi Bawendi, the researchers showed that they could get quantum dots inside human cells grown in the lab, without the particles becoming confined in endosomes or clumping together. They are now working on getting the dots to tag specific proteins inside the cells.

The researchers are also exploring the possibility of using the new system for vaccination. In theory, scientists could remove immune cells from a patient, run them through the microfluidic device and expose them to a viral protein, and then put them back in the patient. Once inside, the cells could provoke an immune response that would confer immunity against the target viral protein.

The research was funded by the National Institutes of Health and the National Cancer Institute.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Tough biogel structures produced by 3-D printing
Researchers have developed a new way of making tough — but soft and wet — bio-compatible materials, called “hydrogels,” into complex and intricately patterned shapes.
Wednesday, June 03, 2015
Designing Better Medical Implants
A team of MIT researchers have discovered a novel method for reducing the typical immune system rejection response when implanting biomedical devices into the body.
Wednesday, May 20, 2015
Mechanically Stimulating Stem Cells
MIT biological engineering graduate student Frances Liu is studying ways to alter mechanical properties of cell environments to produce desired chemical outputs.
Tuesday, March 24, 2015
Proteins Drive Cancer Cells To Change States
When RNA-binding proteins are turned on, cancer cells get locked in a proliferative state.
Monday, December 15, 2014
Finding a Needle in a Haystack
New technique allows scientists to identify populations of rare stem cells in bone marrow.
Wednesday, October 08, 2014
Researchers Unlock a New Means of Growing Intestinal Stem Cells
Studying these cells could lead to new treatments for diseases ranging from gastrointestinal disease to diabetes.
Monday, December 02, 2013
Solving the Mysteries of Regeneration
Biologist Peter Reddien seeks to understand planarians’ famous ability to grow new body parts.
Thursday, August 22, 2013
Two MIT Professors Named Howard Hughes Medical Institute Investigators
Peter Reddien and Aviv Regev are among 27 top biomedical scientists selected nationwide.
Friday, May 10, 2013
Precisely Engineering 3-D Brain Tissues
New design technique could enable personalized medicine, studies of brain wiring.
Thursday, November 29, 2012
Success of Engineered Tissue Depends on Where it’s Grown
Cells grown on different types of scaffolds vary in their ability to help repair damaged blood vessels.
Monday, August 20, 2012
Adult Brain Neurons Can Remodel Connections
The findings could lead to creating growth in cells and regions normally unable to repair themselves.
Tuesday, December 02, 2008
Biologists Theorize Role for DNA Packaging in Stem Cell Development
MIT biologists have discovered that the organization of DNA's packing material plays a critical role in directing stem cells to become different types of adult cells.
Monday, November 10, 2008
Cancer Cells Enlist Adult Stem Cells to Promote Metastasis
Researchers show that some breast cancer cells recruit normal adult stem cells and force them to invade distant tissues.
Friday, October 05, 2007
Team Finds Way to Create Cancer Stem Cells
MIT scientists and colleagues have found a way to create in the lab large amounts of cancer stem cells, or cells that can initiate tumors.
Friday, August 17, 2007
MIT Creates 3D Scaffold for Growing Stem Cells
Stem cells grew, multiplied and differentiated into brain cells on a three-dimensional scaffold of tiny protein fragments designed.
Monday, January 08, 2007
Scientific News
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
New Material Forges the Way for 'Stem Cell Factories'
Researchers have discovered the first fully synthetic substrate with potential to grow billions of stem cells. The researchcould forge the way for the creation of 'stem cell factories' - the mass production of human embryonic (pluripotent) stem cells.
Liver Regrown from Stem Cells
Scientists have repaired a damaged liver in a mouse by transplanting stem cells grown in the laboratory.
Immunotherapy Shows Promise for Myeloma
A strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
'Google Maps' for the Body
Scientists have revealed research that uses previously top-secret technology to zoom through the human body down to the level of a single cell that could be a game-changer for medicine.
Adaptimmune's Novel Cancer Therapeutics Show Positive Clinical Trial Results
The company has announced that positive data from its Phase I/II study of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in patients with multiple myeloma has been published.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!