It has been long recognized that the cytoplasm is a gel, even before the classic book by Frey-Wyssling [1]. Textbooks continue to emphasize the cytoplasm's gel-like consistency, and several groups have recently gone on to describe the functional relevance of the gel-sol transition [2,3]. Researchers working on actin filaments in particular have focused on the cytoplasm's gel-like behavior [4], as have some groups concerned with cellular metabolism [5]. There can be little doubt that the cytoplasm has the consistency of a gel.Yet virtually all cell biological mechanisms build on the principle of free diffusion in aqueous solution. One merely needs to examine representative mechanistic pathways to note the many diffusional steps required in proceeding from stimulus to action. These steps invariably include: ions diffusing into and out of channels; ions diffusing into and out of pumps; ions diffusing through the cytoplasm; proteins diffusing toward other proteins; and substrates diffusing toward enzymes. A cascade of multiple diffusional steps underlies nearly every intracellular process-notwithstanding the cytoplasm's character as a gel, where diffusion can be extremely slow.Surrounding this aqueous intracellular "solution" is the impermeant cell membrane, which restricts the passage of ions and other solutes to flow largely through an array of channels and pumps. Well over 100 solute-specific channels have been identified, with new ones emerging regularly. The same goes for pumps: Since ion concentrations inside and outside the cell are rarely in electrochemical equilibrium, the observed intracellular concentrations are maintained by active pumping. For pump and channel systems to operate, ions require free access.These concepts are certainly familiar to most readers of this journal. For others, the text by Alberts et al.[6] provides a detailed review of this foundational paradigm-along with the manner in which this paradigm accounts for basic cell function. Key words: phase-transition, polymer gel, cell, structured water, cooperativity, movement.Abstract: That the cell is a gel is broadly acknowledged. Textbooks begin with this assertion-and then proceed with great abandon to derive mechanisms based on free diffusion, as though the gel concept were groundless and cell was an aqueous solution. This disconnect emerges in part because the behavior of gels is not well understood, particularly among most biologists. Recently, great strides have been made in the understanding of gel behavior. It has become clear, for example, that a central mechanism in gel function is the phase-transition-a qualitative structural change prompted by a subtle change of environment, not unlike the transition from ice to water. Phase-transitions are capable of doing work. If the cell is a gel, then a logical approach to understanding cell function is to understand gel function-especially whether some role may be played by the phase-transition. Here we pursue this approach. We first consider the dichotomy of the cell as a gel and the cell...