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 Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>