Nonlinear Nanoscale Electrical Transport Distinguishes Fibroblasts and Osteoblasts

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.