SCT: How Small Can a Cell Get?

Cells fit in a “Goldilocks” size
range that enables optimum
function. How did that evolve?

This article was published in Science & Culture Today.

Engineering Places Constraints on Cell Size
that Evolution Cannot Explain
by David Coppedge
Science & Culture Today, November 3, 2026

Why don’t cells grow as big as tennis balls? Why can’t they shrink down to infinity? Science can suggest functional explanations to answer these questions. A tennis-ball sized cell would have too much volume and too many molecules for efficient operation; it would also be more subject to rupture. A nanometer-scale cell could not house the minimum number of enzymes for life. Like a limit on the number of college students able to fit in an old-fashioned telephone booth or a Volkswagen bug, a cell too small would squeeze its genome down too far to operate.

Scientists, therefore, can spin just-so stories about why cells are the way they are: if they were different, they couldn’t function. Functional explanations, however, do not address the reason cells arrived at the optimum size in the first place.

In the 1990s, there was a brief flurry of news about so-called nanobes — possible life forms a tenth the size of the smallest known bacterium. Some of the hype stemmed from tiny structures found in the Mars meteorite ALH84001 that over-eager astrobiologists initially thought might be relics of Martian organisms. Additional structures from rocks in Australia were used to support the claim. By 2001, the hype died down. The Wikipedia page Nanobe relates that “the main criticism of nanobes is that they appear too small to contain the biochemical machinery needed to sustain life.” The page contains links to the original papers and refutations. In short, life as we know it, with its requirements for nucleic acids, proteins, and lipids, has a lower size limit.

Pursuing Scientific Nuance with Evolutionary Clumsiness

A more nuanced investigation into cell size constraints appeared in PNAS this year. “How Small Can a Cell Be?” asked Stanford biologists Shicong Xie and Jan M. Skotheim in a Commentary. They point out that “Enlarged cells can suffer from cytoplasmic dilution, altered proteome composition, replication stress, and increased susceptibility to senescence.” That sets an upper limit on size. “Small cells should face a different set of constraints,” on the other hand. “They must physically fit their genome, ribosomes, organelles, cytoskeletal structures, and the molecular machinery required for growth and division into a smaller space.” To first order, the larger the genome, the larger the cell needs to be. Diploid cells need more room than haploid cells. Nevertheless, “we do not know what goes wrong when cells get too small.”…

Click here to continue reading about what happened when
scientists used “directed evolution” to reduce the size of yeast cells.