Tip penetration through lipid bilayers in atomic force microscopy

In studies of solid supported lipid bilayers with atomic force microscopes (AFM) the force between tip and bilayer is routinely measured. During the approach of the AFM tip in aqueous electrolyte first a short-range repulsive force is observed. For many solid-like and some liquid-like lipid bilayers a subsequent break-through is observed. We observe such a break-through also for dioleoyloxypropyl-trimethylammonium chloride (DOTAP) which is expected to be liquid-like. Here we describe a model which assumes that the jump reflects the penetration of the AFM tip through the lipid bilayer. The model predicts a logarithmical dependence of the break-through force on the approaching velocity of the AFM tip. Two parameters are introduced: The ratio A/alphaV, alpha being a geometric factor, A being the area over which pressure is exerted on the bilayer, 17 the activation volume, and k(0) the rate of spontaneous fort-nation of a hole in the lipid bilayer that is big enough to allow the break-through of the tip. Experiments with bilayers consisting or DOTAP and dioleoylphosphatidylserine (DOPS) show that the break-through forces behave in the predicted way. For DOTAP we obtain ratios A/aV of about 58 nm(-1) and rates k(0) ranging from 1.9 x 10(-8) to 2.5 x 10(-4) s(-1). For DOPS the corresponding values are 162 nm(-1) and 2.0 s(-1). (C) 2002 Elsevier Science B.V. All rights reserved.