Measurement of cell microrheology by magnetic twisting cytometry with frequency domain demodulation

Magnetic twisting cytometry (MTC) (Wang N, Butler JP, and Ingber DE, Scienc e 260: 1124-1127, 1993) is a useful technique for probing cell micromechani cs. The technique is based on twisting ligand-coated magnetic microbeads bo und to membrane receptors and measuring the resulting bead rotation with a magnetometer. Owing to the low signal-to-noise ratio, however, the magnetic signal must be modulated, which is accomplished by spinning the sample at similar to 10 Hz. Present demodulation approaches limit the MTC range to fr equencies <0.5 Hz. We propose a novel demodulation algorithm to expand the frequency range of MTC measurements to higher frequencies. The algorithm is based on coherent demodulation in the frequency domain, and its frequency range is limited only by the dynamic response of the magnetometer. Using th e new algorithm, we measured the complex modulus of elasticity (G*) of cult ured human bronchial epithelial cells (BEAS-2B) from 0.03 to 16 Hz. Cells w ere cultured in supplemented RPMI medium, and ferromagnetic beads (<similar to>5 mum) coated with an RGD peptide were bound to the cell membrane. Both the storage (G', real part of G*) and loss (G ", imaginary part of G*) mod uli increased with frequency as omega (alpha) (2 pi X frequency) with alpha approximate to 1/4. The ratio G " /G' was similar to0.5 and varied little with frequency. Thus the cells exhibited a predominantly elastic behavior w ith a weak power law of frequency and a nearly constant proportion of elast ic vs. frictional stresses, implying that the mechanical behavior conformed to the so-called structural damping (or constant-phase) law (Maksym GN, Fa bry B, Butler JP, Navajas D, Tschumperlin DJ, LaPorte JD, and Fredberg JJ, J Appl Physiol 89: 1619-1632, 2000). We conclude that frequency domain demo dulation dramatically increases the frequency range that can be probed with MTC and reveals that the mechanics of these cells conforms to constant-pha se behavior over a range of frequencies approaching three decades.