Animal Cells: Size Matters

A recent short review^† in Science drew attention to a question that must have been the subject over the years of many a discussion in lab coffee rooms, during those long minutes hanging around between taking samples, or even while staring down a microscope where the phenomenon is so evident: why and how do particular cell types maintain a particular size?

Such conversations I recall ranged from the utilitarian (‘for student practicals always get sections from x* the cells are much bigger) to the theoretical, with the latter being based on the scaling of volume and surface area, and the length of diffusion pathways. Some even recall being asked at university entrance interviews in the 1950s and early 1960s the question: Why are protozoa not bigger?

For those of us who have tried to unravel what happens to the cell population in the mammary gland during pregnancy, lactation and involution, the question of what controls the size of cells has always been at the back of our minds.

Miriam Ginzberg, Ran Kafri and Marc Kirschner, echo the famous J.B.S Haldane essay, ‘On being the right size’ , in the title of their review, ‘On being the right (cell) size’. In their own words, they set out what they tried to achieve:

Different animal cell types have distinctive and characteristic sizes. How a particular cell size is specified by differentiation programs and physiology remains one of the fundamental unknowns in cell biology. In this Review, we explore the evidence that individual cells autonomously sense and specify their own size. We discuss possible mechanisms by which size-sensing and size-specification may take place. Last, we explore the physiological implications of size control: Why is it important that particular cell types maintain a particular size? We develop these questions through examination of the current literature and pose the questions that we anticipate will guide this field in the upcoming years.

It is very easy to find examples of differences in cell size. I turned and pulled down the first book I could find with anything on histology in it. It was the Chester Jones classic monograph, The Adrenal Cortex^‡ and I soon found note of a difference in cell size:

Zona reticularis…The cells themselves are smaller than those of the rest of the cortex… And here are his micrographs that illustrate the difference:

Photomicrographs taken at the same magnification of
cells of three zones of the adrenal cortex of the adult
female rat. Rearranged from Plate I of Chester Jones's
The Adrenal Cortex (1957)

I will not deal with the observations and evidence they considered but conclude with the questions the authors ask:

How is the mean cell size established for each lineage? How do cells adapt to external stimuli to change the set point for their size? How does each cell measure its size and assess its deviation from the mean? By what mechanism do proliferating cells alter their rates of growth or passage through the cell cycle to prevent the natural accumulation of size variability? How do size changes affect cell function, and do certain cells function best at a given size? What role does cell size play in pathology and senescence?

The final question is raised because malignant cancer cells are larger and more variable in size than normal cells.

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†M. B. Ginzberg et al., Science 348, 1245075 (2015). DOI: 10.1126/science.1245075

*I do not remember the species!

‡Chester Jones, I. 1957. The Adrenal Cortex. Cambridge University Press