Scientists find the key to cellular movement

US scientists have said that a key to cellular movement is to regulate the electrical charge on the interior side of the cell membrane, potentially paving the way for understanding cancer, immune cell and other types of cell motion.

The team’s experiments in immune cells and amoebas show that an abundance of negative charges lining the interior surface of the membrane can activate pathways of lipids, enzymes and other proteins responsible for nudging a cell in a certain direction. Their findings, described in the journal Nature Cell Biology, are said to advance biologists’ understanding of cell movement and could help explain the biological processes associated with movement.

“Our cells are moving within our body more than we imagine,” said Peter Devreotes, a professor at the Johns Hopkins University School of Medicine. “Cells move to perform many functions, including when they engulf nutrients or when they divide.”

Many of the molecules involved in cell movement become activated in the leading edge of the cell, or where it forms a kind of foot, or protrusion, that orients the cell in a particular direction. But Johns Hopkins graduate student Tatsat Banerjee began to notice that the negatively charged lipid molecules that line the inner layer of cell membranes were not uniform, as scientists previously thought. Rather, these molecules consistently leave the regions where a cell makes a protrusion.

Banerjee had a hunch that a general biophysical property, such as electrical charge, rather than a specific molecule, could be stimulating and organising the activities of enzymes and other proteins related to cell movement. To test this idea, he and Devreotes used a biosensor — a fluorescently labelled, positively charged peptide — to survey the inner lining of the membrane of human immune cells (macrophages) which engulf invading cells, as well as a single-celled, soil-dwelling amoeba called Dictyostelium discoideum.

They found that when and where the cells formed protrusions, there was a corresponding reduction of negative electrical charge along the inner membrane. Along the cells’ resting membrane surface, the electrical charge increased, which contributes in recruiting more positively charged proteins.

The researchers also engineered novel highly charged, genetically encoded molecules that can be moved within the cell with light. Wherever the scientists shined a light on the cell, new protrusions would form or suppress to move the cell in a certain direction, depending on whether surface charge was decreased or increased. Devreotes said these experimental results are possibly the first proof that the level of generic membrane surface charge has a causal role in controlling cell signalling and motility.

Collaborating with the Johns Hopkins Whiting School of Engineering, the researchers built a computational model to demonstrate how small changes in electrical charges on the inner membrane affect cell signalling activities. Banerjee stated, “The negative surface charge seems to be sufficient and necessary to activate a cascade of biomolecular reactions that have been linked to cell movement.”

Next, the scientists are planning to study precisely how and when the electrical charges are reduced along the inner membrane in response to external cues and how, exactly, the negative charges connect with the complicated protein and lipid signalling networks that prompt cell movement and other associated physiological processes.

Image credit: iStock.com/Jezperklauzen

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