Chapter 16: Magnetic manipulation for force measurements in cell biology.

Life is a mechanical process. Cells, tissues, and bodies must act within their environments to grow, divide, move, communicate, and defend themselves. The stiffness and viscosity of cells and biologic materials will vary depending upon a wide variety of variables including for example environmental conditions, activation of signaling pathways, stage of development, gene expression. By pushing and pulling cells or materials such as mucus or extracellular matrix, one can learn about their mechanical properties. By varying the conditions, signaling pathways or genetic background, one can also assess how the response of the cell or material is modulated by that pathway. Magnetic particles are available commercially in many useful sizes, magnetic contents, and surface chemistries. The variety of surface chemistries allow forces to be applied to a specimen through specific linkages such as receptors or particular proteins, allowing the biologist to ask fundamental questions about the role of those linkages in the transduction of force or motion. In this chapter, we discuss the use of a magnetic system designed to apply a wide range of forces and force patterns fully integrated into a high numerical aperture inverted fluorescence microscope. Fine, thin and flat magnetic poles allow the use of high magnification microscope objectives, and flexible software to control the direction and pattern of applied forces supports a variety of experimental situations. The system can be coupled with simple video acquisition for medium-bandwidth, two-dimensional particle tracking. Alternatively, the system can be coupled with a laser tracking and position feedback system for higher resolution, high bandwidth, three-dimensional tracking.