Computational modelling of cellular geometry effects on chloride channel sensitivity to external electric fields

The aim of this study is to investigate the influence of externally applied electric fields on chloride channel (CLC) function. COMSOL software was used to simulate six distinct cell geometries with 1,000 membrane patches, modeling the spatial distribution of induced electric fields. The simulations quantified how variations in cell geometry influence electric fields and chloride channel behaviour. A range of voltages was applied to assess bilayer lipid membrane response and evaluate how field variations correlate with ion channel activity. Statistical analysis revealed a significant effect of cell geometry on field distribution and chloride channel function. At a constant electric field of 0.1 mV/m, membrane geometry significantly altered chloride channel responses (p < 0.0001). Tukey’s test indicated that curvature and shape influenced field distribution, affecting patch voltage across cell types. Lymphocyte and columnar cells exhibited patch currents of 8.317 pA and 8.314 pA, respectively. These findings provide insights into the role of cell morphology in chloride channel function, with implications for diseases linked to abnormal cell shape and ion channel dysfunction, aiding therapeutic strategies [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] . Our numerical simulations reveal that cell geometry exerts a direct influence on the performance of chloride channels in the cell membrane. Specifically, changes in cell shape alter the distribution of the electric field across the membrane, which in turn modulates the opening or closing behaviour of these channels. These numerical findings underscore that cell geometry is a key parameter for accurate electrophysiological modeling, highlighting the importance of detailed geometric modeling in achieving more precise predictions of channel behaviour.