We describe a recently reported method for directly applying a known, nanonewton-scale force to the nucleus in a living, intact cell. First, a suction seal is applied on the nuclear surface using a micropipette. Then, the micropipette is translated away from the nucleus. The nucleus deforms and translates with the moving micropipette and then eventually detaches from the micropipette and recovers (roughly) its original shape and position. At the point of detachment, the resisting force (from the deformed nucleus and connected cytoskeleton) balances the suction force. Because the suction force is precisely known and reproducibly applied, this method therefore allows comparisons of nuclear response across disruptions to the cytoskeleton, nucleus, or cell. This method is useful for quantifying nuclear elastic properties in its native, integrated environment.
