Scientists Illuminate Life’s Workings By Calculating The Number Of Protein Molecules In A Single Cell

Have you ever wondered how many protein molecules are contained within a single cell? Well, you should – after all, life is nothing without proteins and all their forms, from antibodies and enzymes to storage components and messengers. The world without proteins is like a book without words.

Knowing how many proteins are contained within the average cell is pretty important – particularly when it comes to understanding how certain diseases emerge – but curiously, up until this point, this number has proven to be elusive. Now, after a fairly complex attempt to find the answer, a team led by the University of Toronto (UoT) has finally settled on a figure: 42 million.

Clearly, that’s a lot, and the team over at ScienceAlert has gleefully, and quite rightly, made references to the Meaning of Life, at least the one touted by Douglas Adam’s magnum opus, The Hitchhiker’s Guide to the Galaxy.

As reported by their paper in Cell Systems, it’s actually surprisingly difficult to count these proteins – and not because they had to find each individual molecule by hand. Imagine losing count on something that laborious.

As explained in an accompanying press release, the best researchers have been able to do in the past is add fluorescent tags to protein molecules en masse, a little like a friendly carpet bomb of glow stick fluid. Individual proteins couldn’t be counted, but the general number could be estimated.

A variety in the ways of detecting this fluorescence, and the imprecision in which their numbers were tallied up, always gave a wide array of results, depending on the research laboratory.

Fluorescing proteins within yeast cells. Brandon Ho

Proteins, described by the authors as the “final arbiter of most cellular functions,” are too important to be subjected to guesswork, so they decided to sort this madness out.

The team turned to baker’s yeast (Saccharomyces cerevisiae), a microbe whose simplicity makes it relatively easy to study. In fact, yeast is often the focus of a lot of genetics and microbiology research, including recent attempts to entirely synthesize its genome in a laboratory.

We also happen to have a catalog of every single one of the proteins encoded by its 6,000 genes, which means that – along with known information about the chemical makeup of proteins – the total number of protein molecules per cell could be worked out.

It took 21 studies’ worth of data, but the protein molecule abundance within a single yeast cell was found to be the fabled 42 million, on average.

“I’ve been interested to see the focus on the total number. I like that focus from a curiosity perspective – everyone likes to count things,” co-author Professor Grant Brown of UoT, told IFLScience.

Ultimately, though, it’s the “knowledge of the population of proteins can tell you what kind of cell you are looking at,” and that’s the real highlight of this research.

With that in mind, around 67 percent of the cell’s proteins are composed of 1,000 to 10,000 molecules; others are made of just 10, whereas some are comprised of 500,000.

In any case, this is the most comprehensive picture of the proteome – the entire set of proteins expressed by an organism – in history. Understanding the proteome illuminates how cells age, how they respond to their surrounding environment, how genetic disorders arise, and more. Nailing down this number, then, is no small feat.

One gram of yeast contains about 20 billion yeast cells. That means that tiny amount contains 840,000 trillion protein molecules – far, far more than there are stars in the Milky Way. As ever, the world of the small proves to be mindblowing.

Admittedly, this number is still an estimate, and as pointed out by CBC News, the work was “entirely computational,” but it’s the most robust one yet. Don’t forget, this also only applies to yeast cells, for now.

“Human cells are of course considerably more complex than yeast, and have a much bigger proteome,” Brown adds. “It is also difficult to say what the typical human cell even is.”

We’re sure that number will come in time. Hopefully, unlike the Answer to the Ultimate Question of Life, the Universe, and Everything in Hitchhiker’s, it won’t take 7.5 million years to work out.

Read more: