Untitled

Abstract

At the present time we do not have a theoretical understanding of the physics of cytoplasm. For the greater part of the last century, cell biologists reflexively accepted the physicochemistry of the cell as an extension of reductionist classical thermodynamics. This meant that the physics of the cell was viewed as a collection of random events obeying the laws of statistical mechanics, and its chemistry viewed essentially as a collection of test-tube reactions. During the 1990s however, this general view became overshadowed, and eventually replaced, by more holistic approaches. The awarding of the Nobel Prize to Boyer and Walker in 1997 for mapping the molecular structure and function of ATP synthase carried with it the implication that biologists of all persuasions accepted their model, thereby legitimizing molecular modeling of protein machines as a scientific method. However, biologists utilizing these methods ignore basic energetic questions concerning the role of the medium in stabilizing their machines, and even more importantly, the medium's role as an active participant in molecular mechanisms. On the reverse side of the same proverbial coin, the failure of the IBM Blue Gene Project launched in 1999 to solve protein structure using the classical approach of free energy minimization, revealed the inability of thermodynamics to answer questions concerning the inner workings of biological processes. Here too, the approach ignored water's role in generating physical forces exerted at the molecular level. In this review, I highlight fundamental problems with the current understanding of cytoplasm requiring urgent attention from physicists willing to approach the topic from a new perspective.