Direct Force Measurement of Liposomes by Atomic Force Microscopy


K.Y. Simon Ng Department of Chemical Engineering and Materials Science, Wayne State University

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Liposomes serve as models for cells and show increasing applications in medical and nonmedical fields. Unilamellar vesicles are prepared from multilamellar vesicle (MLV) dispersions either by sonication or extrusion. The shape stability of liposomes is important in the understanding of membrane fusion, as well as in drug delivery and gene therapy. Therefore it has been the subject of numerous theoretical and experimental studies. Atomic force microscopy (AFM) images a surface by scanning a sharp tip attached to a cantilever at a close distance to the surface. AFM is the newest tool for liposome study because it provides nanoscale analysis of liposome shape and mechanical properties simultaneously. AFM provides surface topographical images with spatial resolution close to 1 Å and force-vs.-distance curves with detection limit close to 10− 12 N. AFM has become the preferred method for imaging soft materials such as molecular crystals, proteins, and living cells. This entry describes new features of adsorbed vesicles by AFM investigation. AFM imaging and force measurement were conducted simultaneously in liquid on adsorbed but intact unilamellar vesicles with sizes less than 50 nm. The unilamellar vesicles were made by sonication from egg yolk phosphatidylcholine (EggPC) dispersion. The AFM tip can be moved on top of individual vesicles so that mechanical properties of the smallest vesicles can be measured at the nanometer scale. The EggPC vesicle undergoes reversible shape changes from convex to flattened and concave shape with increasing image force. In addition to the monotonic repulsion because of vesicle resistance to the AFM tip advancement and compression, there exist several characteristic breaks in the force-vs.-distance curves. Hertz analysis of the slope of repulsion gives a measure of vesicle elastic properties. The Young's modulus (E) and the bending modulus (kc) of the adsorbed EggPC vesicles were measured to be (1.97 ± 0.75) × 106 Pa and (0.21 ± 0.08) × 10− 19 J, respectively. The breaks in the force curve are interpreted as the tip jumping across the bilayer.