Thermodynamics predicts that transmembrane voltage modulates membrane tensi
on(1) and that this will cause movement. The magnitude and polarity of move
ment is governed by cell stiffness and surface potentials. Here we confirm
these predictions using the atomic force microscope to dynamically follow t
he movement of voltage-clamped HEK293 cells(2) in different ionic-strength
solutions. In normal saline, depolarization caused an outward movement, and
at low ionic strength an inward movement. The amplitude was proportional t
o voltage (about 1 nm per 100 mV) and increased with indentation depth. A s
imple physical model of the membrane and tip provided an estimate of the ex
ternal and internal surface charge densities (-5 x10(-3) C m(-2) and -18x10
(-3) C m(-2), respectively). Salicylate (a negative amphiphile(3)) inhibite
d electromotility by increasing the external charge density by -15x10(-3) C
m(-2). As salicylate blocks electromotility in cochlear outer hair cells a
t the same concentration(4,5), the role of prestin as a motor protein(6) ma
y need to be reassessed.