Cells' electric fields keep nanoparticles at bay, scientists confirm

The humble membranes that enclose our cells have a surprising superpower: They can push away nano-sized molecules that happen to approach them. A team including scientists at the National Institute of Standards and Technology (NIST) has figured out why, by using artificial membranes that mimic the behavior of natural ones. Their discovery could make a difference in how we design the many drug treatments that target our cells.

The team's findings, which appear in the Journal of the American Chemical Society, confirm that the powerful electrical fields that cell membranes generate are largely responsible for repelling nanoscale particles from the surface of the cell.

This repulsion notably affects neutral, uncharged nanoparticles, in part because the smaller, charged molecules the electric field attracts crowd the membrane and push away the larger particles. Since many drug treatments are built around proteins and other nanoscale particles that target the membrane, the repulsion could play a role in the treatments' effectiveness.

The findings provide the first direct evidence that the electric fields are responsible for the repulsion. According to NIST's David Hoogerheide, the effect deserves greater attention from the scientific community.

"This repulsion, along with the related crowding that the smaller molecules exert, is likely to play a significant role in how molecules with a weak charge interact with biological membranes and other charged surfaces," said Hoogerheide, a physicist at the NIST Center for Neutron Research (NCNR) and one of the paper's authors. "This has implications for drug design and delivery, and for the behavior of particles in crowded environments at the nanometer scale."

Membranes form boundaries in nearly all kinds of cells. Not only does a cell have an outer membrane that contains and protects the interior, but often there are other membranes inside, forming parts of organelles such as mitochondria and the Golgi apparatus. Understanding membranes is important to medical science, not least because proteins lodged in the cell membrane are frequent drug targets. Some membrane proteins are like gates that regulate what gets into and out of the cell.

The region near these membranes can be a busy place. Thousands of types of different molecules crowd each other and the cell membrane—and as anyone who has tried to push through a crowd knows, it can be tough going. Smaller molecules such as salts move with relative ease because they can fit into tighter spots, but larger molecules, such as proteins, are limited in their movements.

This sort of molecular crowding has become a very active scientific research topic, Hoogerheide said, because it plays a real-world role in how the cell functions. How a cell behaves depends on the delicate interplay of the ingredients in this cellular "soup." Now, it appears that the cell membrane might have an effect too, sorting molecules near itself by size and charge.

"How does crowding affect the cell and its behavior?" he said. "How, for example, do molecules in this soup get sorted inside the cell, making some of them available for biological functions, but not others? The effect of the membrane could make a difference."