Cell Membrane Capacitance (Cm) Measured by Bioimpedance Spectroscopy (BIS): A Narrative Review of Its Clinical Relevance and Biomarker Potential

Abstract

Cell membrane capacitance (C_m) is a potential biomarker that reflects the structural and functional integrity of cell membranes. It is essential for physiological processes such as signal transduction, ion transport, and cellular homeostasis. In clinical practice, C_m can be determined using bioimpedance spectroscopy (BIS), a non-invasive technique for analysing the intrinsic electrical properties of biological tissues across a range of frequencies. C_m may be relevant in various clinical fields, where high capacitance is associated with healthy and intact membranes, while low capacitance indicates cellular damage or disease. Despite its promise as a prognostic indicator, several knowledge gaps limit the broader clinical application of C_m. These include variability in measurement techniques (e.g., electrode placement, frequency selection), the lack of standardised measurement protocols, uncertainty on how C_m is related to pathology, and the relatively low amount of C_m research. By addressing these gaps, C_m may become a valuable tool for examining cellular health, early disease detection, and evaluating treatment efficacy in clinical practice. This review explores the fundamental principles of C_m measured with the BIS technique, its mathematical basis and relationship to the biophysical Cole model, and its potential clinical applications. It identifies current gaps in our knowledge and outlines future research directions to enhance the understanding and use of C_m. For example, C_m has shown promise in identifying membrane degradation in sepsis, predicting malnutrition in anorexia nervosa, and as a prognostic factor in cancer.

Keywords: bioimpedance; bioimpedance spectroscopy; biomarker; cells; electrical impedance; membrane capacitance.

Figure 1

A simple equivalent parallel electrical circuit for biological tissue, representing two distinct components. The upper branch models the intracellular pathway, where current crosses the double-layered cell membrane (electrically represented by the capacitance C_m) and passes through the intracellular water (ICW, electrically represented by the resistance R_I). The lower branch represents the extracellular compartment, characterised by R_E, the resistance of the extracellular water (ECW). More complex models have been developed, but these provide minimal practical advantage [2].

Figure 2

A simplified depiction of electric current flow in body tissues. At high frequencies, the current travels through both the extracellular water (ECW) and intracellular water (ICW), collectively representing the total body water (TBW). In contrast, low-frequency currents cannot cross cell membranes and are confined to the ECW.

Figure 3

A parallel-plate capacitor and a biological cell membrane are both capacitors. The capacitor (left) stores charge (+Q, −Q) across a dielectric barrier, generating a displacement current. Its capacitance is C = ϵA/d, where ϵ is the dielectric constant, A is the plate area, and d is the plate separation. Similarly, the cell membrane (right) acts as a capacitor, with the phospholipid bilayer as the dielectric barrier.

Figure 4

A Cole plot illustrating the impedance (Z) of biological tissue as a combination of resistance (R) and capacitive reactance (X_C), varying with frequency. Strictly, the reactance X_C of a capacitor is negative, but by convention, the Cole plot is plotted with X_C as positive [23]. The impedance vector forms a phase angle (θ) with R, indicating the phase shift between the applied voltage and current. The rightmost point (R_E or R₀) represents low-frequency resistance, reflecting the extracellular water (ECW). In contrast, the leftmost point (R_INF or R_∞) corresponds to high-frequency resistance, encompassing both the ECW and intracellular water (ICW), indicative of the total body water (TBW). The characteristic frequency (f_c) at the plot’s peak marks where cell membrane capacitance (C_m) significantly affects current flow, with R_E in parallel with R_I and C_m, as shown in Figure 1. Due to distribution effects (e.g., cell size and shape), biological tissues exhibit alpha dispersion factor (α) values between 0 and 1. Mathematically, α < 1 causes the centre point of the semi-circle to be suppressed below the R axis [8].