Horacio Cantiello

Atomic force microscopy (AFM) is a unique 3D surveying technique with an atomic resolution that offers a novel approach to exploring the properties of surfaces. Unlike other microscopy techniques, AFM acts as a scanning probe that directly interacts with the surface atoms of the sample, providing a more direct and detailed view. It can be modified to investigate various surface properties such as friction, adhesion forces, mechanical and viscoelastic properties, and image magnetic or electrostatic properties. One of its most potent adaptations is surface potential microscopy (SPoM), which allows for the simultaneous measurement of surface potential (VDC) and surface topography. This unique capability of AFM has revolutionized the study of nanostructural details and biomechanical properties of biological samples, including biomolecules and cells, in live samples in liquid media. AFM can analyze various samples in controlled atmospheres, including polymers, adsorbed molecules, films, and fibers. Despite its enormous potential, many biologists interested in structure-function correlations still need to become familiar with the applications and techniques of AFM.

In the present review, we summarize our experience with AFM in studying ion channels of medical interest and their essential interactions with different elements of the cytoskeleton and membrane lipids. Surface potential microscopy (SPM) and AFM have become indispensable tools for elucidating structure-function correlations in biological systems, particularly in transient receptor potential (TRP) channels and cytoskeletal dynamics. In TRP channels, AFM has provided novel insights into ion channel function and interactions with membranes. For example, Chasan et al. (2002) observed the direct interaction between actin and the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, highlighting its role as a regulator of the cytoskeleton in ion channel function, demonstrating that ion channels could act as proteins actin couplers ("Actin-Binding-Protein"), creating a structure-function interface between the ion channel and the cytoskeleton. Furthermore, Goldmann et al. (2005) confirmed that the actin cytoskeleton dynamics are easily explorable by temporally tracking AFM samples in the solution of actin-myosin complexes. In parallel, combining AFM and SPM has revolutionized the study of cytoskeletal dynamics. Zhang and Cantiello (2009) used SPM to map the electrical properties of microtubules and actin bundles, revealing information about the charge distribution in the structural organization of polymers.