Nav: Home

Vesicle formation findings could pave way for liquid biopsies, drug delivery devices

March 06, 2017

Engineers at Carnegie Mellon University and biomedical researchers at the University of Pittsburgh and Magee-Womens Research Institute have established a framework for understanding the mechanics that underlie vesicle formation. Their findings, published in the online early edition of the Proceedings of the National Academy of Sciences, can be used to help develop liquid biopsies for a range of diseases and to develop new drug delivery vehicles.

The researchers are collaborating on a project funded by the National Institutes of Health that is attempting to create a non-invasive diagnostic tool for pregnancy abnormalities, reducing the need for amniocentesis. During pregnancy, vesicles are released from the placenta into the mother's blood stream. In addition to biological markers, the physical properties of these vesicles, such as their size, rigidity and viscosity, also may hold clues to potential complications of pregnancy, including fetal growth restriction and other placental disorders.

The Magee researchers, led by Yoel Sadovsky, are collecting experimental data on vesicles, and are characterizing their biological and biochemical properties and cargo. The Carnegie Mellon engineers, including Subra Suresh, K. Jimmy Hsia, David Quinn and Changjin Huang, are exploring new ways in which an understanding of the vesicles' basic biophysical properties can be used to develop better clinical practices and outcomes.

"Developing a comprehensive framework of how vesicles form, using fundamental principles of science and engineering, has the potential to suggest new approaches to diagnostics and therapeutics for human diseases, " said Suresh, president of Carnegie Mellon and a co-author of the research. "This study provides a quantitative understanding of the conditions under which vesicles form, which may not only help in the design of synthetic drug delivery devices, but also provide insights into how the physical characteristics of vesicles could be altered by diseases."

In biological systems, vesicles bring material in and out of the cell. They are formed when a lipid bilayer membrane folds in to create a container around the material that is being transported. The vesicle's properties, including its size and viscosity, may change in response to disease.

To understand the interconnection between a vesicle's size, structure and properties, the researchers looked at the basic thermodynamics and energetics that drive vesicle formation. Experimental results from the Magee team suggest that some of the most interesting and useful biological cargo of vesicles may be contained in exosomes, the smallest of three major vesicle types, with diameters of approximately 100 nanometers. The Carnegie Mellon team found that the folding process in these smallest vesicles is highly nonlinear. The researchers then used nonlinear mechanics and thermodynamics to establish connections between the lipid structure, curvature and resulting vesicle size and shape.

Through their calculations, the researchers accurately predicted the size distribution of vesicles in a sample, with their results matching experimental results of other research groups. They also are able to predict a cup-like configuration of vesicles that has been observed experimentally, but could not be predicted on the basis of existing standard linear theory.

"Gaining this fundamental level of understanding allows us to see if there is a correlation between the biophysical properties and the structures of the vesicles," said Hsia, a professor of biomedical and mechanical engineering at Carnegie Mellon. "From there we can begin to derive what's going on in the system and associate the changes with disease states."

This heightened understanding of vesicles' biophysical properties means that researchers potentially can use new cell separating technologies to remove vesicles from a simple blood sample. Such technologies, like an acoustic cell sorting device being developed by a collaboration between Carnegie Mellon, the Massachusetts Institute of Technology and Duke University, are considered "liquid biopsies" and offer a non-invasive alternative to traditional biopsy techniques.

"Our discoveries shed new light on vesicle-based non-hormonal communication among tissues," said Sadovsky, director of the Magee-Womens Research Institute. "Harnessing the power of engineering tools will allow researchers to design new, non-invasive diagnostic tools that can change our definition of health and wellness during pregnancy and other periods of human development."

In addition, establishing the fundamental mechanisms behind vesicle formation provides new parameters that researchers can use to optimize the size of artificial vesicles for the creation of new drug delivery vehicles.
This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD086325) and Carnegie Mellon University.

Carnegie Mellon University

Related Pregnancy Articles:

Paracetamol during pregnancy can inhibit masculinity
Paracetamol during pregnancy can inhibit masculinity Paracetamol during pregnancy can inhibit the development of 'male behavior' in mice.
The cost of opioid use during pregnancy
A new study published today by the scientific journal Addiction reveals that the incidence of neonatal abstinence syndrome -- often caused by mothers using opioids during pregnancy -- is increasing in the United States, and carries an enormous burden in terms of hospital days and costs.
New study: Pre-pregnancy BMI directly linked to excess pregnancy weight gain
It's well known that excessive weight gain during pregnancy can have a lasting negative impact on the health of a mother and her baby.
Pregnancy-specific β1-glycoproteins
Development of new strategies and novel drug design to treat trophoblastic diseases and to provide pregnancy success are of crucial importance in maintenance the female reproductive health.
Should hypothyroidism in pregnancy be treated?
When a woman becomes pregnant, many changes occur in her body.
Pre-pregnancy progesterone helps women with recurrent pregnancy loss
Women who have had two or more unexplained miscarriages can benefit from natural progesterone treatment before pregnancy, a new a study from the University of Illinois at Chicago shows.
Male pipefish pregnancy, it's complicated
In the upside-down world of the pipefish, sexual selection appears to work in reverse, with flashy females battling for males who bear the pregnancy and carry their young to term in their brood pouch.
Pregnancy leads to changes in the mother's brain
A study directed by researchers from the UAB and IMIM are the first to reveal how pregnancy causes long-lasting alterations in brain structure, probably related to improving the mother's ability to protect and interact with the child.
MRIs during pregnancy and outcomes for infants, children
In an analysis that included more than 1.4 million births, exposure to magnetic resonance imaging (MRI) during the first trimester of pregnancy compared with nonexposure was not associated with increased risk of harm to the fetus or in early childhood, although gadolinium MRI at any time during pregnancy was associated with an increased risk of a broad set of rheumatological, inflammatory, or skin conditions and, possibly, for stillbirth or neonatal death, according to a study appearing in the Sept.
The benefits of exercise during pregnancy
Women who exercise during pregnancy are more likely to deliver vaginally than those who do not, and show no greater risk of preterm birth.

Related Pregnancy Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...