The human body is a sophisticated organism that has complex internal communication systems down to a cellular level. However, these systems transmit more than just messages about healthy human functions; they can also influence disease.
Cells can “talk” to their neighbors by passing small particles called exosomes
Consider cancer. Jinglei Ping poses the question: “How do unhealthy cells transport their own cancer information to the nearby cells to have the tumor grow and finally turn into cancer?”
More importantly, can the conversation be controlled to stop the disease?
Ping, an assistant professor of mechanical and industrial engineering at the University of Massachusetts Amherst, with an adjunct role in biomedical engineering and affiliation with the Institute for Applied Life Sciences, will use his $1.9 million, five-year grant to attempt to answer these questions.
The Maximizing Investigators’ Research Award from the National Institutes of Health will support Ping’s investigation into a new way to manipulate cell communication, with implications for developing therapeutics to treat cancer and heart disease.
One way cells “talk” to their neighbors is by passing small particles called exosomes.
“Exosomes are very small ‘bubbles’ generated by cells and the bubbles deliver important molecules, like RNA or small pieces of DNA, from one cell to another,” Ping explains.
However, this mechanism can also explain the spread of disease within the body.
“Exosome release is related to the growth of tumor cells and how tumors become cancer,” he says.
Similarly, cells that control the heartbeat, known as cardiomyocytes, are also influenced by exosome traffic, with implications for heart disease.
By controlling the exosomes, new therapies may be possible, and Ping wants to use pH, which represents the concentration of hydrogen ions in a substance, to connect the dots.
“Exosome traffic controls the signal of the cells—they are the cell messengers,” he says. “And the traffic can be controlled by the pH, so the question is: How can we control pH precisely?”
Current chemical methods of changing the pH in a cell’s environment rely on diffusion, which has two major drawbacks. First, it’s not targeted, so you can’t pinpoint which cells you want to affect. And it’s slow—it may take hours to diffuse into the cell and make changes.
“You have no idea when the cell actually started to respond to the pH variation because you cannot control the delivery of hydrogen ions,” he explains.
Adding an acid or a base to a solution isn’t the only way to change its pH—Ping has demonstrated that this can also be accomplished by passing a well-controlled electric current through it. With this grant, Ping aims to further develop an array of microelectrodes, each creating its own pH microenvironment, to regulate exosome-based communications between cell clusters at highly precise locations.
“It changes it from a chemical process to an electronic process so it’s quick and it’s controllable.”
He says that there are many important applications of this work.
“It could be very useful, for example, to view new phenomenon in biology, shed light on tissue engineering and also drug delivery.”
With this in mind, his research will focus on developing this method of controlling exosomes specifically for tumor cells and cardiomyocytes.
Source – University of Massachusetts Amherst