Nav: Home

Artificial fluorescent membrane lipid shows active role in living cells

June 05, 2017

Osaka, Japan - Biological membranes, such as those surrounding animal cells, are made up of lipids and proteins. Because these molecules do not usually mix well, they are distributed within different regions of the membrane. This segregation is achieved in a number of ways, including the formation of domains based on particular lipids such as cholesterol or sphingomyelin (SM). These two lipids are required for the generation of cholesterol-dependent raft domains, which are necessary for signaling within the plasma membrane. However, it was not clear how SMs interacted with other molecules of raft domains, mainly because of the lack of a suitable synthetic probe of SM. Now, research led by Osaka University in collaboration with JST ERATO Lipid Active Structure Project has developed new fluorescent synthetic molecules (analogs) that structurally mimic SMs and can be studied in live cells. The study was reported in J Cell Biol.

Existing fluorescent SM analogs behave differently from their fully functional natural counterparts. For example, they usually separate into a different type of fluid phase from that seen in living membranes. Moreover, those synthetic analogs that do split into the correct fluid phase produce a weak fluorescent signal, quickly lose their pigment, or sometimes need to be excited by UV light.

Researchers at Osaka University overcame these limitations with fluorescent SM analogs by joining several fluorescent chemical compounds (fluorophores) that were highly hydrophilic to the hydrophobic lipid part (mainly acyl chains) of the synthetic molecule. "We took care to ensure that the positive charge of the headgroup was maintained by not modifying its lipid part," co-first author Masanao Kinoshita says. "This was achieved by keeping the fluorescent compounds away from the headgroup using a long linker component."

After confirming that the synthetic molecules behaved similarly to natural SM by using simple model membranes, the team next used highly sensitive single-molecule imaging to monitor the role of SMs in living cell membranes.

"We observed interactions of the SM analogs with each other and with CD59, which is a type of lipid receptor that is commonly used to link proteins to the plasma membrane," corresponding author Nobuaki Matsumori says. "These interactions were shown to sometimes require the presence of cholesterol as well as an alcohol component of SMs."

Further analysis revealed the dynamic behavior of SMs as they rapidly associated and dissociated from raft domains involving different formations of CD59 and with the plasma membrane. These findings may help in modifying future molecular interactions such as increasing their rate or complexity.
-end-


Osaka University

Related Cholesterol Articles:

Experimental cholesterol-lowering drug effective at lowering bad cholesterol, study shows
Twice-yearly injections of an experimental cholesterol-lowering drug, inclisiran, were effective at reducing low-density lipoprotein (LDL) cholesterol, often called bad cholesterol, in patients already taking the maximum dose of statin drugs, according to data of the ORION-10 trial presented Saturday, Nov.
Rethinking how cholesterol is integrated into cells
Cholesterol is best known in connection with cardiovascular disease, but cholesterol is also vital for many fundamental processes in the body.
Seed oils are best for LDL cholesterol
Using a statistical technique called network meta-analysis, researchers have combined the results of dozens of studies of dietary oils to identify those with the best effect on patients' LDL cholesterol and other blood lipids.
Cholesterol leash: Key tethering protein found to transport cellular cholesterol
Cholesterol is an essential component of living organisms, but the mechanisms that transport cholesterol inside the cell are poorly understood.
New way to treat cholesterol may be on the horizon
A breakthrough discovery by scientists at Houston Methodist Research Institute could change the way we treat cholesterol.
How low should LDL cholesterol go?
New analysis shows that in a high-risk population, achieving ultra-low LDL cholesterol levels, down to <10 mg/dL, safely results in additional lowering of risk of cardiovascular events.
Does boosting 'good' cholesterol really improve your health?
A new review addresses the mysteries behind 'good' HDL cholesterol and why boosting its levels does not necessarily provide protection from cardiovascular risk for patients.
Researchers zero-in on cholesterol's role in cells
For the first time, by using a path-breaking optical imaging technique to pinpoint cholesterol's location and movement within the cell membrane, chemists at the University of Illinois at Chicago have made the surprising finding that cholesterol is a signaling molecule that transmits messages across the cell membrane.
Raising 'good cholesterol' not as effective as lowering 'bad cholesterol'
Low and very high levels of HDL, or 'good cholesterol' are associated with a higher risk of dying from heart disease, cancer and other causes, according to a study today in the Journal of the American College of Cardiology.
New gene for familial high cholesterol
New research from Denmark reveals the gene that explains one quarter of all familial hypercholesterolemia with very high blood cholesterol.
More Cholesterol News and Cholesterol Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.