According to the scientists, the surface electric charge on the inner side of its membrane plays a key role in cell motility.
Johns Hopkins Medicine scientists say a key to cell movement is the regulation of electrical charge on the inner side of the cell membrane, potentially paving the way for understanding cancer, immune cells and other types of cell movement. Experiments in immune cells and amoebas show that an abundance of negative charges on the inner surface of the membrane can activate pathways for lipids, enzymes and other proteins responsible for nudging a cell in a certain direction .
The findings, described in the October issue of Nature Cell Biology, advance biologists’ understanding of cell movement and potentially help explain biological processes associated with movement, such as how cancer cells move and they spread beyond the original site of a tumor and how immune cells migrate to areas of infection or wound healing.
“Our cells move around in our bodies more than we imagine,” says Peter Devreotes, professor in the Department of Cell Biology at Johns Hopkins University School of Medicine. “Cells move to perform many functions, including ingesting nutrients and dividing.” Many of the molecules involved in cell movement are activated at the leading edge of the cell, where it forms a foot, or protrusion, that orients the cell in a particular direction.
Tatsat Banerjee, also a Johns Hopkins biomolecular researcher and lead author of the study, began to notice that the negatively charged lipid molecules lining the inner layer of cell membranes weren’t uniform, as scientists previously thought. He noticed that this set of molecules was constantly moving away from the regions where a cell has the ledge. Banerjee guessed that a general biophysical property, such as electric charge, rather than a specific molecule, could stimulate and organize the activities of enzymes and other proteins related to cell movement. To test this idea, Banerjee and Devreotes used a biosensor, a fluorescently labeled and positively charged peptide, to detect the inner membrane lining of human immune cells, called macrophages, which engulf invasive cells, and a single-celled soil-dwelling amoeba called Dictyostelium discoideum .
They found that when and where the cells formed protrusions, there was a corresponding reduction in negative electrical charge along the inner membrane. Alternatively, along the resting membrane surface of the cells, the electrical charge increased , helping to recruit more positively charged proteins. Johns Hopkins researchers have also designed new highly charged, genetically encoded molecules that can be moved within the cell with light . Wherever the scientists illuminated the cell, new protrusions were formed or suppressed to move the cell in a certain direction, depending on whether the surface charge was decreased or increased.
Devreotes says these experimental results are perhaps the first evidence that membrane surface charge level plays a role in the control of cell signaling and motility .
In collaboration with Pablo Iglesias and his research group from the Department of Electrical and Computer Engineering at the Johns Hopkins Whiting School of Engineering, the researchers built a computational model to demonstrate how small changes in the electrical charges of the inner membrane affect the signaling activities cell phone. “The negative surface charge appears to be sufficient and necessary to activate a cascade of biomolecular reactions that have been linked to cell movement,” says Banerjee.
Next, the scientists plan to study precisely how and when electrical charges are reduced along the inner membrane in response to external stimuli and how, exactly, the negative charges connect to the complicated protein and lipid signaling networks that stimulate cell movement and other associated physiological processes.
- Spatiotemporal dynamics of membrane surface charges regulates cell polarity and migration (nature.com)