LSA talked with Biophysics Professor Sarah Veatch about how proteins moving in membranes can help cells communicate with the outside world. Veatch worked with collaborators Matt Stone (Ph.D. ‘16), research fellow Sarah Shelby, Ph.D. student Marcos Núñez, and research lab specialist Kathleen Wisser.

Can you give some background about what you’ve been studying?

Sarah Veatch: A thin layer of lipids and proteins surrounds all cells, forming each cell’s plasma membrane. The membrane layer acts as both a boundary and a communication gatekeeper, separating the cell from the outside world. Because it participates in these key roles, the membrane is a part of the cell that hosts a broad array of cellular biochemistry. It’s an environment that controls how the proteins embedded within it interact in time and space.

Special experimental membranes, isolated from cells, also can contain coexisting liquid phases—similar to the separation of oil and water—and proteins in the membrane sometimes preferentially associate with one or the other liquid phase.

What were you trying to figure out with your research?

SV: For decades, people have been wondering how protein associations with a particular liquid phase could influence the way those proteins interact and signal in cells. But studying this kind of thing in intact cell membranes is difficult! Largely because features in cell membranes are small and hard to visualize.

We’ve investigated how protein associations with liquid phases can regulate protein signaling interactions, using the membranes of B cells, a type of white blood cell involved in immune responses.

What did you find out?

SV: We showed that the preference of proteins for different liquid phases affects how they organize and function within the plasma membrane. We found that this type of membrane-mediated interaction can create regions of the cell membrane where proteins aggregate or are excluded. When these regions form, a cell can more effectively respond to its environment. These changes in the membrane can tip the balance of biochemical networks that are active at the cell surface, making certain reactions more likely to happen.

What does this mean for the way cells communicate?

SV: Cell membranes are the interface between the outside world and the inner workings of cells. For the cell to do something that impacts the cells around it, or to sense something that’s going on in its environment, information has to somehow pass through the cell membrane. Our work shows that cells have more tools at their disposal than we thought to make those messages happen.

This is particularly useful for immune cells, because these cells don't have the option of responding to only one type of stimulus—they have to be able to respond to many different types of molecules and invaders, ranging in size from single proteins to bacteria to tumors.

Could your findings impact the way we treat diseases?

SV: We think that cells can become more sensitive or less sensitive to stimuli just by changing the properties of their membrane. This strategy could come in handy if a cell wants to put the brakes on some reaction—for example, maybe a cell doesn’t want to respond if its energy stores are low, or maybe the cell wants to be ready for some event that it expects will happen soon.

These cell membrane changes can also be associated with disease. The protein interactions we study are linked to some cancers because these signaling pathways can lead to cell growth and division. If it’s true that changes in the membrane are at least partially responsible for changes in the sensitivity of these protein interactions, then we could have a whole new way of approaching the treatment of diseases that cause this type of cellular dysfunction.

The group's full paper is available on eLife.

Image: A typical B cell. Clockwise from left: (1) Proteins (red and green spots) in the cell membrane, chemically frozen in place. (2) When cells are alive, proteins move around on the cell surface. Red and green lines show the paths of the proteins. (3) Proteins moving in a live cell explore different parts of the membrane, creating fields of color over time (red and green), rather than spots. (4) Position of proteins in the cell membrane (red and green spots), estimated using a mathematical model.