What is it about?
Why cells are small and don’t grow indefinitely large? This study explores how cell size influences growth and metabolism in human cells. By analyzing a diverse panel of cancer cell lines, the researchers discovered that larger cells grow slower because cell size dictates the rates at which cells take up nutrients and release waste metabolites. Specifically, when cells increase in size, waste removal declines more slowly than nutrient uptake, which limits the growth of larger cells. The study also identifies a maximum cell size where growth stops - not because metabolism shuts down, but because cells reach a balance where the mass of the waste metabolites they throw out equals the mass of the metabolites as they take in.
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Photo by National Cancer Institute on Unsplash
Why is it important?
Understanding why cell growth slows with increasing cell size helps explain how cells maintain their dimensions—and what goes wrong in diseases like cancer, where cells grow uncontrollably. This research also challenges the long-held belief that the surface area of the cell limits how fast cells can take in nutrients. Instead, this work suggests that specific metabolic bottlenecks, particularly the demand for electron acceptors like aspartate, play a bigger role in limiting cell enlargement. Overall, these findings could inform research in cancer biology, where uncontrolled growth is a hallmark, and in developmental biology, where cell size is thought to be critical for tissue function.
Perspectives
This research was an exciting journey from the very beginning as we realized that our large-scale analysis of cancer cell lines is starting to reveal new information about how cell size shapes metabolism and how this may be related to the well-known allometric scaling of metabolism in organisms. Looking ahead, I’m fascinated by how these principles might explain not only the growth of cancer cells but also normal development and diseases linked to mitochondrial dysfunction. Finally, I hope these findings spark new ideas beyond our original questions to move science forward.
Mikael Bjorklund
Read the Original
This page is a summary of: Establishment of cell size–dependent growth rate via differential scaling of metabolite uptake and release, Proceedings of the National Academy of Sciences, June 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2425347122.
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