Manipulating the genetic identity and biochemical surface properties of individual cells with electric-field-induced fusion

A method for cell-cell and cell-liposome fusion at the single-cell level is described. Individual cells or liposomes were first selected and manipulat ed either by optical trapping or by adhesion to a micromanipulator-controll ed ultramicroelectrode. Spatially selective fusion of the cell-cell or cell -liposome pair was achieved by the application of a highly focused electric field through a pair of 5-mu m o.d. carbon-fiber ultramicroelectrodes. The ability to fuse together single cells opens new possibilities in the manip ulation of the genetic and cellular makeup of individual cells in a control led manner, In the study of cellular networks, for example, the alteration of the biochemical identity of a selected cell can have a profound effect o n the behavior of the entire network. Fusion of a single liposome with a ta rget cell allows the introduction of the liposomal content into the cell in terior as well as the addition of lipids and membrane proteins onto the cel l surface. This cell-liposome fusion represents an approach to the manipula tion of the cytoplasmic contents and surface properties of single cells. As an example, we have introduced a membrane protein (gamma-glutamyltransfera se) reconstituted in liposomes into the cell plasma membrane.