Investigating cell functioning by theoretical analysis of cell-to-cell variability.

Here we discuss cell-to-cell variability in isogenic cell populations on the basis of an analogy between the processes of vesicle self-reproduction and cell self-replication. A short review of the theoretical analysis of vesicle self-reproduction is presented to indicate that this process only occurs under the fulfillment of specific criteria: causal relations between the values of vesicle variables involved in its growth and division, and the parameters of the environment. It is shown that when division is asymmetric, both vesicle birth size and interdivision times are variable. We argue that during cell self-replication, the balance between processes of cell growth and division also relies on causal relations between the corresponding cellular variables. A possible method is suggested to unravel previously unidentified causal relations between cell variables from the relationships between their variability parameters such as the widths of their probability distributions and their correlation coefficients. The method is outlined by reviewing the results of the corresponding analysis applied to a population of red blood cells. Some novel research directions are suggested that could lead from the analysis of cell-to-cell variability to a better understanding of the organizational structure of cells and possibly also their evolutionary origin.