Seeing cells, and why they stay small

Most cells are far too small to see with the naked eye. Cell sizes are measured in micrometers (µm); a micrometer is a thousandth of a millimeter. Bacteria are usually 1–10 µm across and a typical plant or animal cell is 10–100 µm, so studying cells means using a microscope, a tool that magnifies small objects. An image taken through a microscope is a micrograph.

Three things that make a good image

Resolution is the measure of clarity, and it sets the real limit on what a microscope can show. Each microscope has a useful range of magnification. Beyond it, the image just gets bigger and blurrier, the way zooming in on a fuzzy phone photo gives you a bigger fuzz instead of new detail.

Light vs. electron microscopes

Microscopes fall into two groups by what they shine on the sample:

• A light microscope uses visible light. The best ones can distinguish objects about 0.2 µm apart.
• An electron microscope uses a beam of electrons. An electron beam has a much shorter wavelength than light (its waves are packed far closer together), and shorter waves pick out finer detail. Typical electron microscopes resolve objects about 0.1 nanometer (nm) apart, roughly 2,000 times better. (A nanometer is a thousandth of a micrometer.)

That difference decides what you can see. Cells and their larger internal parts show up in a light microscope, but a virus is too small; you’d need an electron microscope. Light microscopes keep improving through better lenses, sample preparation, lighting, and computer image processing, which has produced many specialized types.

Electron microscopes come in two main types. In transmission electron microscopy (TEM), electrons pass through a thin slice of the sample, and the image forms from the ones that make it through. In scanning electron microscopy (SEM), the beam sweeps across the sample’s surface, and the image forms from electrons knocked off that surface.

A newer, lens-free method, electron ptychography, fires electrons at an object from many angles and lets a computer rebuild an image from the way they scatter. It has reached a resolution below 0.02 nm, finer than the width of a hydrogen atom.

Why cells stay small

Small size is nearly universal among cells. An elephant isn’t big because its cells are big: most of them are about the size of a mouse’s cells, and the elephant simply has far more.

The reason lies at the cell’s surface. Everything a cell imports (nutrients) and exports (wastes) must cross its outer boundary, the plasma membrane. How much the cell needs depends on its volume, but how fast it can exchange depends on its surface area. So what matters is the surface area/volume ratio.

For a sphere of radius r:

• surface area = 4πr², which grows with the square of the radius
• volume = (4/3)πr³, which grows with the cube of the radius

As a cell gets bigger, its volume outpaces its surface area, and the surface area/volume ratio falls. A large cell would have too little membrane to supply its interior. That’s the leading explanation for why most cells stay small: only a high ratio lets the membrane bring in nutrients and ship out wastes fast enough.

Shape matters too

Cells can work around the limit by being long and thin, or by having a folded, irregular surface. Compare a round cell of radius 21 µm with a cylinder-shaped cell only 3 µm in radius but 1,372 µm long. Both hold about 38,800 µm³, yet the cylinder’s surface area/volume ratio (about 0.67) is nearly five times the sphere’s (about 0.14).

That’s one reason a neuron (nerve cell), with its long, branching extensions, can be so large. The same logic explains why surfaces that absorb nutrients, like the lining of the intestine, are highly folded.

Check yourselfYou want to look at a virus. Which microscope do you need, and why?

An electron microscope. Most viruses are smaller than the roughly 0.2 µm resolution limit of light microscopes, while electron microscopes resolve detail about 2,000 times finer.