For cellular biosynthesis and metabolism, size matters

How does cell size affect its contents and energy usage? A new frontier in cell biology highlights the importance of understanding the relationship between cell size and two major cellular processes: biosynthesis and metabolism.

Cell size is a fundamental concept that can affect many different areas of research. Senescence and enlarged cells are key markers of aging, while non-homogenous cell size can indicate cancerous growth. Understanding how cell size affects its processes could also help answer a fundamental question about life: why did cells evolve to be a certain size?

The lab of Professor Rebecca Heald at the University of California, Berkeley explores mechanisms of cell division and size control. Clotilde Cadart, a postdoctoral researcher in the Heald lab, is interested in how cell size relates to metabolism and recently published a perspective article in Molecular Biology of the Cell to bring attention to this line of inquiry.

As Cadart describes it, “When cells are too big, the processes that allow the parallel increase of all cellular components (proteins, fat, etc.) fail, causing cells to become sick and eventually die. It’s a bit like trying to make a bigger cake without increasing the amounts of all ingredients in the correct proportions: the cake texture could change, or it could be less tasty!”

Previous research on cell size has focused primarily on biosynthesis, or in Cadart’s analogy, “adding the correct amounts of all the cake ingredients.” An untapped frontier lies in the relationship between cell size and metabolism, that is, the energy production in making a cake. While doubling a cake’s size might double the cake ingredients (biosynthesis), “some steps—like putting the icing on top—do not increase with the cake volume but with cake surface area.”

How does the concentration of components and the energy used scale with cell size? This is the knowledge gap Cadart and Heald hope to bring more attention to.

Cell size, in general, is determined by the relative rates of cell growth and division, but there are many open questions about how cell size influences organismal physiology. While mostly unexplored, some of the known metabolic cell scaling phenomena include:

• Mitochondrial efficiency is optimal in immortalized human cell lines at intermediate sizes.
• Human stem cells with half the genome content (haploids) express oxidative-phosphorylation genes at higher levels than normal diploids.
• The metabolic rate in unicellular organisms becomes less efficient the larger the cell becomes.

To further the analogy, an ideally-sized cake has the most scrumptious ratio of icing to filling. Similarly, perhaps, variation in cell dimensions can change the ratio of its contents in ways that alter cell function and metabolism to be more or less optimal.

While research is underway to understand single-cell scaling relationships, researchers must connect this information with tissue and whole-organism physiology. To address the lack of knowledge surrounding the effect of cell size on biosynthesis and metabolism at a larger scale, many disciplines with diverse backgrounds will need to collaborate. As Cadart says, “theoreticians, cell and organismal biologists, experts in metabolism as well as cell size regulation, ecologists, and evolutionary biologists…. a whole community will be needed!”  

Cadart and Heald are currently delving into this field using frog embryos and hope to translate their work to compare across species with different genome sizes.