Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Detecting lysosomal pH with better fluorescent probes

10.04.2015

Lysosomes are the garbage disposals of animal cells. As the resources are limited in cells, organic materials are broken down and recycled a lot -- and that's what lysosomes do. Detecting problems with lysosomes is the focus of a new set of fluorescent probes developed by researchers at Michigan Technological University. The Royal Society of Chemistry published their work in January.

"A lot of diseases are related to problems with lysosome functions," says Jingtuo Zhang, a chemistry doctoral candidate at Michigan Tech. Zhang and his advisor, Haiying Liu, have developed the new probes, essentially chemical dyes that illuminate lysosome structures with fluorescence.


New fluorescent dyes help illuminate lysosome structures.

Credit: Jingtuo Zhang

"These kinds of lysosome probes respond to pH, and that gives us a more clear idea of a cell's health," Zhang says.

Responding to different acidic conditions within lysosomes is a unique feature of the new probes. This is important because small changes in pH can reflect much bigger problems. Currently, few commercially available lysosome fluorescent probes are sensitive to pH.

Additionally, the fluorescence is near-infrared. That means the probes emit light that can penetrate deeper than commercial dyes, making for better bio-imaging of lysosome structures.

These dyes have minimal toxicity. Much like chemotherapy, imaging lysosomes comes at a cost -- the chemicals can be toxic. The team decreased toxicity by creating new molecules, a process called synthesis.

"Designing a molecule is an art, and synthesis is our toolkit," Zhang explains. He goes on to describe the molecules created by the team using a core of boron dipyrromethene, or BODIPY.

Rings of carbon make up the bulk of BODIPY, like a three-legged stool. The working part of the core is a section with fused carbon rings, nitrogen, boron and fluoride. The BODIPY edges then are modified by piperazine rings. Finally, the team connected long chains. All together, the probe is a leggy molecule centered on the BODIPY rings, trailing flexible carbon chains kinked with oxygens that look like strands of a 1980s Toni Home Perm.

That permed legginess is actually crucial. The oxygen-rich chains make the molecules more water soluble, making it easier on the body and for bio-imaging applications. The piperazine addition then targets lysosome cells specifically, allowing the BODIPY core to do its work in the right place and fluoresce.

In the fluorescent images, the chemicals appear as glowstick-bright colors.

"There are clear dot structures when we zoom in on the images," Zhang says, pointing out where the green and red colors have concentrated in the rounded lysosome structures outside the blue nucleus.

Ideally, he explains, the team wants to see orange, which shows where their probes and popular commercial dyes overlap in the lysosomes. The overlap is good, indicating the probes are indeed targeting the right cellular structure. Ashutosh Tiwari, an assistant professor of chemistry at Michigan Tech, is particularly interested in those orange zones.

Tiwari worked with Zhang and Liu to apply their synthesized probes and oversaw the cell cultures and testing. He says the team is trying to balance the chemical's impact on the cell without losing its lysosome-targeting and fluorescent functionality.

"That would be a win-win situation, but in reality it's really a trade off of certain features," Tiwari says, adding the low toxicity and near-infrared features are definite wins.

The researchers are currently looking to commercialize their product. They also plan to continue making modifications to the BODIPY fluorescent probes to further enhance the lysosome targeting and lower the toxicity even further.

Media Contact

Allison Mills
awmills@mtu.edu
906-487-2343

 @michigantech

http://www.mtu.edu 

Allison Mills | EurekAlert!

More articles from Life Sciences:

nachricht Magic number colloidal clusters
13.12.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Record levels of mercury released by thawing permafrost in Canadian Arctic
13.12.2018 | University of Alberta

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Magic number colloidal clusters

13.12.2018 | Life Sciences

UNLV study unlocks clues to how planets form

13.12.2018 | Physics and Astronomy

Live from the ocean research vessel Atlantis

13.12.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>