recent additions:

Mijailovich SM, Kojic M, Zivkovic M, Fabry B, Fredberg JJ. A finite element model of cell deformation during magnetic bead twisting. J Appl Physiol 93:1429-1436, 2002
PDF-version (816 KB)

Butler JP, Tolic-Norrelykke IM, Fabry B, Fredber JJ. Traction fields, moments, and strain energy that cells exert on their surroundings. Am J Physiol Cell Physiol 282:C595–C605, 2002.
PDF-version (608 KB)

Magnetic twisting cytometry (MTC) was developed at the Physiology Program of the Harvard School of Public Health. Using MTC, controlled mechanical stresses can be applied to specific cell surface receptors using ligand-coated ferromagnetic beads. MTC can:

1. apply controlled mechanical stress to cells;
2. assay for ligand-receptor adhesion strength;
3. assay for mechanical linkages between a cell surface receptor and the cytoskeleton;
4. assay for the mechanical (rheological) properties of the cytoskeleton (such as stiffness or shear modulus, viscosity, and motility); and
5. assay for intracellular biochemical changes such as remodeling of the cytoskeleton.

Applying mechanical forces and stresses to cells, (in order to measure cellular mechanics, or cell rheology) using magnetic beads is a surprisingly old idea, dating back to the beginning of the 20^th century.

Magnetic dragging and twisting was put on a solid scientific ground first by Francis H.C. Crick. (He is better known for his pioneering efforts to determine the three-dimensional structures of large molecules found in living organisms, however, during World War II, Crick worked as a physicist in the development of magnetic mines for use in naval warfare). His paper (together with A. F. W. Hughes) "The physical properties of cytoplasm" in Experimental Cell Research,1:37-80 and "The physical properties of cytoplasm. A study by means of the magnetic particle method. Part II. Theoretical treatment" in Experimental Cell Research,1:505-533 are still essential reading for cell rheology researchers.

For about 20 years following Crick's work, nothing noteworthy (to my knowledge) happened in the field of magnetic twisting (or pulling) cytometry. Things changed in the early 1970th when researchers around Joe Brain at the Harvard School of Public Health and David Cohen from the Francis Bitter Magnetic Laboratory (MIT) got interested in the clearance ability of lung macrophages. They let animals inhale aerosolated ferromagnetic particles, magnetized the particles with a brief magnetic pulse of high intensity, and then measured the magnetic signal decaying over time. This signal decay was interpreted as a result of the phagocytic activity of lung macrophages: The faster the macrophages internalized the foreign magnetic particles, the faster the particles' magnetic orientation would become randomized.

When Peter Valberg and later Jim Butler, both accomplished physicists, arrived at the Harvard School of Public Health, they invented Magnetic Twisting Cytometry to study the mechanical properties and motility of pulmonary macrophages: ferromagnetic particles got "eaten" by a small sample of macrophages, then the particles where magnetized and subsequently twisted in a homogeneous magnetic field. Depending on the macrophages' rheological properties, the magnetic particles rotated faster or slower. This rotation was measured with sensitive fluxgate-magnetometers. Measuring the particles' small magnetic field  (on the order of 1 nTesla) in the presence of a large twisting field (of about 5 mTesla) and magnetic noise from the environment is a formidable engineering problem. Valberg used multiple layers of mu-metal shielding and spun the macrophages in order to use lock-in-amplification of the small magnetic signals.

What if one wants to measure the mechanical properties of cells that do not phagocytose the magnetic beads? The answer is to "glue" the ferromagnetic beads to the cell surface. To this end, Ning Wang from the Harvard School of Public Health and Donald Ingber of Children's Hospital coated the particles with ligands for specific surface receptors. Now almost any cell type could be measured, and moreover the mechanical linkage between the receptor and the cytoskeleton could be probed. Using a computer-controlled machine, it is now possible to continuously measure cell rheology (shear modulus or stiffness, viscosity, motility) over a wide range of frequencies (now between 0.01 and 1000 Hz).

magnetic bead attached to an airway smooth muscle cell

fibroblast on a square pattern