Nannobacteria: size limits and evidence
August 1, 1997: Following the discussion of “nannobacteria” in letters to the Editor of Science by Jack Maniloff, Kenneth H. Nealson, Roland Psenner and Maria Loferer, and Robert L. Folk (1), and by Ralph Harvey in his review for naturalSCIENCE (2), I would like to address some biophysical arguments based on my own studies of selforganizing biomolecules, such as membrane phospholipids, and the general hydration properties of biomolecules.
Theoretical estimates of the minimal diameter for a living cell assume a spherical form and, as the main constituents, proteins, RNA (DNA), lipids and precursors, polysaccharides and precursors, and water. One of the smallest living cells, the mycoplasma, has a diameter of about 0.12 µm (3). On average, the water content of a cell is about 70 percent by weight. Assuming that the densities of all the components are roughly the same; namely, 1000 kg m-3, the weight of a mycoplasma is about 9 * 10-19 kg, including 6.3 * 10-19 kg of water.
For the metabolic processes of a cell to proceed, cellular constituents must have certain structural as well as dynamic properties. If cell water content is reduced from 70% to about 20%, the fluidity of the system may be reduced, but basic cell functions could still be maintained. Many metabolic processes take place at, or close to interfaces, i.e., membranes, at rates that are often diffusion limited. However, in phospholipid membranes, the rate of lateral diffusion of membrane-associated water, membrane lipids, and small molecules can be comparable to that in free solution (4,5). Thus, many metabolic processes can be entirely confined within the quasi two-dimensional membrane “space.” Further evidence consistent with the possibility of functional cells having a water content of 20% or less is the remarkably rapid enzymatic activity of certain frozen protein solutions, in which the quantity of unfrozen water is minimal (6, and references therein).
Thus, if cell water content were only 20%, rather than 70%, the calculated minimum diameter for a spherical cell would be no more than 75 nm. One might anticipate the occurrence of such nanometer-scale cells under extreme conditions, such as may characterize the environment of extraterrestrial life forms.