Nonlinear Nanoscale Electrical Transport Distinguishes Fibroblasts and Osteoblasts

High Resolution Image Download MS PowerPoint Slide Electrical signaling plays a central role in cellular function, yet direct mapping of electrical transport within individual cells at the nanoscale remains challenging. Conventional electrophysiological and impedance-based techniques either lack sufficient spatial resolution or significantly perturb cellular properties. Here, we employ conductive atomic force microscopy (CAFM) to probe effective local current–voltage (I–V) characteristics with subcellular resolution in fixed and air-dried cells from two mammalian cell types: L929 fibroblasts and OFCOLII osteoblasts cultured on conductive indium tin oxide (ITO) substrates. Spatially resolved current maps reveal a systematically enhanced electrical response in nuclear regions compared to the cytoplasmic periphery in both cell types. L929 fibroblasts exhibit predominantly linear, ohmic-like I–V behavior, whereas OFCOLII osteoblasts display pronounced nonlinear, diode-like electrical transport. Quantitative analysis reveals strong cell-type- and region-dependent variations in effective resistance and capacitance, highlighting the role of intracellular organization in shaping nanoscale electrical behavior. These results establish CAFM as a powerful approach for resolving subcellular electrical heterogeneity and demonstrate that distinct electrical transport signatures can differentiate cellular phenotypes at the single-cell level. These findings position nanoscale electrical transport as a physically grounded marker of cellular phenotype.