Conditionally Immortalized Neural Cell Lines: Potential Models for the Study of Neural Cell Function

Studies on primary cell cultures have contributed significantly to our understanding of neural cell function. Nevertheless, for many studies the value of these primary cell cultures has been limited by the time the cultures survivein vitro,the quantity of cellular material available for analysis, and the need to prepare the cells on a regular basis from fresh tissue. Techniques for immortalizing cells have existed for some time, but the repertoire of immortalizing genes has grown significantly. This has expanded our ability to generate useful cell lines of specific neural types that are better models of thein vivophenotype than previously. The constitutive expression of oncogenes keeps cells in a proliferative state that could lead to the loss of differentiated gene expression and function. An appealing improvement of immortalization methodology is the use of temperature-sensitive oncogenes that generate cell lines that can proliferate at a permissive temperature and “differentiate” at a nonpermissive temperature. The proliferation of such conditionally immortalized cell lines can be suppressed simply by increasing the temperature. Cell lines maintained at the nonpermissive temperature can enter into a stage in which they express differentiated properties of the cell. The potential ability of conditionally immortalized neural cell lines to accurately reflect theirin vivofunction has now been demonstrated on several occasions through transplantation experiments. In this report, the generation of these cell lines is described along with a discussion of their potential applications in neurobiology.     

Hybrid Lipids as a Biological Surface-Active Component

Cell membranes contain small domains (on the order of nanometers in size, sometimes called rafts) of lipids whose hydrocarbon chains are more ordered than those of the surrounding bulk-phase lipids. Whether these domains are fluctuations, metastable, or thermodynamically stable, is still unclear. Here, we show theoretically how a lipid with one saturated hydrocarbon chain that prefers the ordered environment and one partially unsaturated chain that prefers the less ordered phase, can act as a line-active component. We present a unified model that treats the lipids in both the bulk and at the interface and show how they lower the line tension between domains, eventually driving it to zero at sufficiently large interaction strengths or at sufficiently low temperatures. In this limit, finite-sized domains stabilized by the packing of these hybrid lipids can form as equilibrium structures.