Mapping the electrostatic profile of cellular membranes.

Anionic phospholipids can confer a net negative charge to biological membranes. This surface charge generates an electrical field that serves to recruit extrinsic cationic proteins, can alter the disposition of transmembrane proteins and causes the local accumulation of soluble counterions, altering the local pH and the concentration of physiologically important ions like calcium. Because the phospholipid composition of the different organellar membranes varies, their surface charge is similarly expected to diverge. Yet, despite the important functional implications, remarkably little is known about the electrostatic properties of the individual organellar membranes. We therefore designed and implemented approaches to estimate the surface charge of the cytosolic membrane of various organelles in situ in intact cells. Our data indicate that the inner leaflet of the plasma membrane is most negative, with a surface potential of approximately -35 mV, followed by the Golgi complex > lysosomes > mitochondria ≈ peroxisomes > the endoplasmic reticulum, in decreasing order.