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 from Brightsurf:

COVID-19 has a prolonged effect for many during pregnancy
Symptoms for pregnant women with COVID-19 can be prolonged, lasting two months or longer for a quarter of the women who participated in a national study led by UC San Francisco and UCLA.

Relaxed through pregnancy
A group of researchers from Charité - Universitätsmedizin Berlin have been able to show that maternal psychological wellbeing during pregnancy has a positive effect on newborn infants.

Trajectories of antidepressant medication use during pregnancy
In an analysis of women who started pregnancy when taking antidepressant medications, investigators identified three trajectories of antidepressant dispensing during pregnancy: more than half stopped their treatment, a quarter maintained their treatment throughout pregnancy, and one-fifth discontinued it for a minimum of three months and then resumed it during the postpartum period.

Are women using e-cigarettes during preconception and/or pregnancy?
A new study of 1,365 racially/ethnically diverse, low-income pregnant women found that 4% reported e-cigarette use.

A better pregnancy test for whales
To determine whale pregnancy, researchers have relied on visual cues or hormone tests of blubber collected via darts, but the results were often inconclusive.

Cannabis use during pregnancy
The large health care system Kaiser Permanente Northern California provides universal screening for prenatal cannabis use in women during pregnancy by self-report and urine toxicology testing.

Questions and answers about cannabis use during pregnancy
A new study shows that women have many medical questions about the use of cannabis both before and during pregnancy, and during the postpartum period while breastfeeding.

The effect of taking antidepressants during pregnancy
Exposure to antidepressants during pregnancy and the first weeks of life can alter sensory processing well into adulthood, according to research in mice recently published in eNeuro.

Is ivermectin safe during pregnancy?
Is it safe to give ivermectin to pregnant women? To answer this question, researchers from the Barcelona Institute for Global Health (ISGlobal), an institution supported by 'la Caixa,' conducted a systematic review and meta-analysis of studies that reported cases of accidental exposure to the drug among pregnant women.

Going to sleep on your back in late pregnancy
This study looked at whether going to sleep on your back in the third trimester of pregnancy was associated with average lower birth weights.

Read More: Pregnancy News and Pregnancy Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to