A new study shows how cells transmit signals across the cell to coordinate migration. The research resolves a long-running debate between proponents of opposing hypotheses by showing that both sides are right.
New research published in Cell shows that cells can send signals from one end of the cell to the other by changing the tension of the cell membrane at one end and propagating this to the other end of the cell, in addition to chemical and electrical signalling.
The forces that change the tension of the cell membrane are an integral part of how cells send information between parts of the cell and how they regulate migration. Thus, this type of cellular communication is an important factor in many ways, including metastasis and the processes that cause a zygote to divide to form a fetus and eventually become a human being.
The research not only sheds light on how cells communicate but hopefully also buries the hatchet between researchers who have held apparently opposing views on this.
“Some researchers thought that cells generate long-range membrane tension propagation, whereas other researchers have found that external forces applied to membranes do not propagate at all. Our research shows that both views are indeed correct,” explains a researcher behind the study, Orion Weiner, Professor, Cardiovascular Research Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, USA,
Researchers have long disagreed
Previous research has suggested that cells can use force to change the tension of the cell membrane to send information from one end of the cell to the other.
One can imagine that a cell needs to migrate in a certain direction and that this requires that the ends of the cell communicate.
Proteins perform tasks in a cell membrane, but proteins only respond to stimuli in their immediate surroundings. The question has therefore been how proteins at one end of a cell membrane can respond to stimuli propagated from the other end.
Some research groups have carried out experiments suggesting that when the cell locally pulls on its own cell membrane (changing the tension), similar to pulling on one end of a balloon, the change in tension is propagated to the other end of the cell membrane and that the proteins there can react to this stimulus.
However, other researchers have applied external force directly to the cell membrane and found that the tension changes do not propagate to the rest of the cell.
“Proteins at one end of the cell ‘know’ what is happening at the other end, but the unsettling question has been whether they sense it through physical forces across the cell membrane, similar to a tug of war, with proteins at one end of the cell sensing that the proteins at the other end are tugging on the rope. If membrane tension does not propagate, it is not a good long-range integrator of cell responses,” says Orion Weiner.
Using advanced technology to study cells
To clarify this question, the researchers from Orion Weiner’s group carried out a series of experiments in collaboration with the Carlos Bustamante Group (University of California, Berkeley) and Herve Turlier’s group (Collège de France, Paris).
First, they used an advanced method to measure the tension in a specific region of a cell membrane by putting a carboxyl latex bead on the cell membrane and measuring how hard the cell membrane pulled back on the bead.
Second, the researchers leveraged optogenetics to insert a light-sensitive protein into the cells’ core. This enabled them to locally control cellular events by shining light on the cells, which could induce the cell to locally push on the cell membrane and change the tension.
This allowed the researchers to investigate whether the effect of the cell tugging on its own membrane differed from the cell membrane being externally pulled.
No researchers wrong
The results show very clearly that the force the cell exerts on the cell membrane very rapidly propagates information to the rest of the cell.
The researchers determined very precisely how the forces propagated by examining different locations on the cell membrane simultaneously,.
The researchers also tried to influence the cell membrane by applying external force, but the tension failed to propagate. They constructed a unifying mathematical model that clarified the requirements for membrane tension propagation in cells.
Orion Weiner and colleagues therefore confirmed both sides in the dispute: the researchers who had found that cells can send signals from one end of the cell to the other by pulling on the cell membrane through internal forces and the researchers who had found that applying external force to the cell membrane had no effect.
“Resolving a controversial research question and having no one be wrong is satisfying; the previous confusion helps to clarify the holes in our understanding,” explains Orion Weiner.
Like tugging on a rug
Orion Weiner says that the discovery provides new insight into the function of the cell membrane and the forces that affect the cell membrane in cellular communication.
He says that the cell membrane and the underlying actin cytoskeleton, which is like a scaffold that maintains cell shape, work together to send signals from one end of the cell to the other.
If you picture the cell membrane as a rug and the underlying actin cytoskeleton as the sticky mat that ensures that the rug does not slide around on the floor, then moving the rug (cell membrane) by tugging may require moving the sticky mat (the actin cytoskeleton) at the same time.
Trying to do this by solely tugging on the rug is equivalent to externally tugging on the cell membrane.
In contrast, the cell applies force to both the cell membrane and the actin cytoskeleton, and this propagates information from one end of the cell to the other.
“The actin cytoskeleton and the membrane work together to transmit signals around the cell. This knowledge of how cells act is important for understanding how membrane tension interfaces with numerous cellular processes, including cancer cells metastasising to new tissue and embryonic cells controlling migration to form tissues and organs,” concludes Orion Weiner.