Organelles

Overview

 

Welcome! I hope the transformation wasn't too alarming. You have shrunk down to about 3 millionths of your normal size. You are now about 0.5 micrometers tall (a micrometer is 1/1000 of a millimeter). But don't worry, you'll return to your normal size before you finish this chapter.

At this scale, a medium-sized human cell looks as long, high, and wide as a football field. But from where we are, you can't see nearly that far. Clogging your view is a rich stew of molecules, fibers, and various cell structures called organelles. Like the internal organs in your body, organelles in the cell each have a unique biological role to play.

Now that your eyes have adjusted to the darkness, let's explore, first-hand and up close, the amazing world inside a cell.

A typical animal cell, sliced open to reveal cross-sections of organelles.

Nucleus: The Cell's Brain

Look down. Notice the slight curve? You're standing on a somewhat spherical structure about 50 feet in diameter. It's the nucleus—basically the cell's brain.

The nucleus is the most prominent organelle and can occupy up to 10 percent of the space inside a cell. It contains the equivalent of the cell's gray matter—its genetic material, or DNA. In the form of genes, each with a host of helper molecules, DNA determines the cell's identity, masterminds its activities, and is the official cookbook for the body's proteins.

Go ahead—jump. It's a bit springy, isn't it? That's because the nucleus is surrounded by two pliable membranes, together known as the nuclear envelope. Normally, the nuclear envelope is pockmarked with octagonal pits about an inch across (at this scale) and hemmed in by raised sides. These nuclear pores allow chemical messages to exit and enter the nucleus. But we've cleared the nuclear pores off this area of the nucleus so you don't sprain an ankle on one.

If you exclude the nucleus, the rest of the cell's innards are known as the cytoplasm. Virtually all forms of life fall into one of two categories: eukaryotes or prokaryotes.

Eukaryotic Cells	Prokaryotic Cells
The cells of “complex” organisms, including all plants and animals	“Simple” organisms, including bacteria and blue-green algae
Contain a nucleus and many other organelles, each surrounded by a membrane (the nucleus and mitochondrion have two membranes)	Lack a nucleus and other membrane-encased organelles
Can specialize for certain functions, such as absorbing nutrients from food or transmitting nerve impulses; groups cells can form large, multicellular organs and organisms	Usually exist as single, virtually identical cells
Most animal cells are 10–30 micrometers across, and most plant cells are 10–100 micrometers across	Most are 1–10 micrometers across

Endoplasmic Reticulum: Protein Clothier and Lipid Factory

If you peer over the side of the nucleus, you'll notice groups of enormous, interconnected sacs snuggling close by. Each sac is only a few inches across but can extend to lengths of 100 feet or more. This network of sacs, the endoplasmic reticulum (ER), often makes up more than 10 percent of a cell's total volume.

 

The endoplasmic reticulum comes in two types: Rough ER is covered with ribosomes and prepares newly made proteins; smooth ER specializes in making lipids and breaking down toxic molecules.

Take a closer look, and you'll see that the sacs are covered with bumps about 2 inches wide. Those bumps, called ribosomes, are sophisticated molecular machines made up of more than 70 proteins and 4 strands of RNA, a chemical relative of DNA. Ribosomes have a critical job: assembling all the cell's proteins. Without ribosomes, life as we know it would cease to exist.

To make a protein, ribosomes weld together chemical building blocks one by one. As naked, infant protein chains begin to curl out of ribosomes, they thread directly into the ER. There, hard-working enzymes clothe them with specialized strands of sugars.

Now, climb off the nucleus and out onto the ER. As you venture farther from the nucleus, you'll notice the ribosomes start to thin out. Be careful! Those ribosomes serve as nice hand- and footholds now. But as they become scarce or disappear, you could slide into the smooth ER, unable to climb out.

In addition to having few or no ribosomes, the smooth ER has a different shape and function than the ribosome-studded rough ER. A labyrinth of branched tubules, the smooth ER specializes in synthesizing lipids and also contains enzymes that break down harmful substances. Most cell types have very little smooth ER, but some cells—like those in the liver, which are responsible for neutralizing toxins—contain lots of it.

Next, look out into the cytosol. Do you see some free-floating ribosomes? The proteins made on those ribosomes stay in the cytosol. In contrast, proteins made on the rough ER's ribosomes end up in other organelles or are sent out of the cell to function elsewhere in the body. A few examples of proteins that leave the cell (called secreted proteins) are antibodies, insulin, digestive enzymes, and many hormones.

Golgi: Finishing, Packaging, and Mailing Centers

Now, let's slog through the cytosol a bit. Notice that stack of a half dozen flattened balloons, each a few inches across and about 2 feet long? That's the Golgi complex, also called the Golgi apparatus or, simply, the Golgi. Like an upscale gift shop that monograms, wraps, and mails its merchandise, the Golgi receives newly made proteins and lipids from the ER, puts the finishing touches on them, addresses them, and sends them to their final destinations. One of the places these molecules can end up is in lysosomes.

Lysosomes: Recycling Centers and Garbage Trucks

See that bubble about 10 feet across? That's a lysosome. Let's go—I think you'll like this. Perhaps even more than other organelles, lysosomes can vary widely in size—from 5 inches to 30 feet across.

Go ahead, put your ear next to it. Hear the sizzling and gurgling? That's the sound of powerful enzymes and acids chewing to bits anything that ends up inside.

But materials aren't just melted into oblivion in the lysosome. Instead, they are precisely chipped into their component parts, almost all of which the cell recycles as nutrients or building blocks. Lysosomes also act as cellular garbage trucks, hauling away unusable waste and dumping it outside the cell. From there, the body has various ways of getting rid of it.

Cool Tools for Studying Cells

Cell biologists would love to do what you just did—shrink down and actually see, touch, and hear the inner workings of cells. Because that's impossible, they've developed an ever-growing collection of approaches to study cellular innards from the outside. Among them are biochemistry, physical analysis, microscopy, computer analysis, and molecular genetics. Using these techniques, researchers can exhaustively inventory the individual molecular bits and pieces that make up cells, eavesdrop on cellular communication, and spy on cells as they adapt to changing environments. Together, the approaches provide vivid details about how cells work together in the body's organs and tissues. We'll start by discussing the traditional tools of the trade—microscopes—then touch on the new frontiers of quantum dots and computational biology.

Light Microscopes: The First Windows Into Cells

Robert Hooke, the British scientist who coined the word "cell," probably used this microscope when he prepared Micrographia. Published in 1665, Micrographia was the first book describing observations made through a microscope. It was a best-seller.

This fireworks explosion of color is a dividing newt lung cell seen under a light microscope and colored using fluorescent dyes: chromosomes in blue, intermediate filaments in red, and spindle fibers (bundled microtubules assembled for cell division) in green.

Scientists first saw cells by using traditional light microscopes. In fact, it was Robert Hooke (1635–1703), looking through a microscope at a thin slice of cork, who coined the word "cell." He chose the word to describe the boxlike holes in the plant cells because they reminded him of the cells of a monastery.

Scientists gradually got better at grinding glass into lenses and at whipping up chemicals to selectively stain cellular parts so they could see them better. By the late 1800s, biologists already had identified some of the largest organelles (the nucleus, mitochondria, and Golgi).
Researchers using high-tech light microscopes and glowing molecular labels can now watch biological processes in real time. The scientists start by chemically attaching a fluorescent dye or protein to a molecule that interests them. The colored glow then allows the scientists to locate the molecules in living cells and to track processes—such as cell movement, division, or infection—that involve the molecules.

Fluorescent labels come in many colors, including brilliant red, magenta, yellow, green, and blue. By using a collection of them at the same time, researchers can label multiple structures inside a cell and can track several processes at once. The technicolor result provides great insight into living cells—and is stunning cellular art.

Electron Microscopes: The Most Powerful of All

In the 1930s, scientists developed a new type of microscope, an electron microscope that allowed them to see beyond what some ever dreamed possible. The revolutionary concept behind the machine grew out of physicists' insights into the nature of electrons.

As its name implies, the electron microscope depends not on light, but on electrons. The microscopes accelerate electrons in a vacuum, shoot them out of an electron gun, and focus them with doughnut-shaped magnets. As the electrons bombard the sample, they are absorbed or scattered by different cell parts, forming an image on a detection plate.

Scanning electron microscopes allow scientists to see the three-dimensional surface of their samples.

Although electron microscopes enable scientists to see things hundreds of times smaller than anything visible through light microscopes, they have a serious drawback: They can't be used to study living cells. Biological tissues don't survive the technique's harsh chemicals, deadly vacuum, and powerful blast of electrons.

Electron microscopes come in two main flavors: transmission and scanning. Some transmission electron microscopes can magnify objects up to 1 million times, enabling scientists to see viruses and even some large molecules. To obtain this level of detail, however, the samples usually must be sliced so thin that they yield only flat, two-dimensional images. Photos from transmission electron microscopes are typically viewed in black and white.

Scanning electron microscopes cannot magnify samples as powerfully as transmission scopes, but they allow scientists to study the often intricate surface features of larger samples. This provides a window to see up close the three-dimensional terrain of intact cells, material surfaces, microscopic organisms, and insects. Scientists sometimes use computer drawing programs to highlight parts of these images with color.

Studying Single Molecules: Connecting the Quantum Dots

Dyes called quantum dots can simultaneously reveal the fine details of many cell structures. Here, the nucleus is blue, a specific protein within the nucleus is pink, mitochondria look yellow, microtubules are green, and actin filaments are red. Someday, the technique may be used for speedy disease diagnosis, DNA testing, or analysis of biological samples.

Whether they use microscopes, genetic methods, or any other technique to observe specific molecules, scientists typically flag every molecule of a certain type, then study these molecules as a group. It's rather like trying to understand a profession—say, teaching, architecture, or medicine—by tagging and observing all the workers in that profession simultaneously. Although these global approaches have taught us a lot, many scientists long to examine individual molecules in real time—the equivalent of following individual teachers as they go about their daily routines.

Now, new techniques are beginning to allow scientists to do just that. One technology, called quantum dots, uses microscopic semiconductor crystals to label specific proteins and genes. The crystals, each far less than a millionth of an inch in diameter, radiate brilliant colors when exposed to ultraviolet light. Dots of slightly different sizes glow in different fluorescent colors—larger dots shine red, while smaller dots shine blue, with a rainbow of colors in between. Researchers can create up to 40,000 different labels by mixing quantum dots of different colors and intensities as an artist would mix paint. In addition to coming in a vast array of colors, the dots also are brighter and more versatile than more traditional fluorescent dyes: They can be used to visualize individual molecules or, like the older labeling techniques, to visualize every molecule of a given type.

Quantum dots promise to advance not only cell biology but also a host of other areas. Someday, the technology may allow doctors to rapidly analyze thousands of genes and proteins from cancer patients and tailor treatments to each person's molecular profile. These bright dots also could help improve the speed, accuracy, and affordability of diagnostic tests for everything from HIV infection to allergies. And, when hitched to medicines, quantum dots might deliver a specific dose of a drug directly to a certain type of cell.

Computers Clarify Complexity

Say you're hungry and stranded in a blizzard: If you eat before you seek shelter, you might freeze to death, but if you don't eat first, you might not have the strength to get yourself out of the storm. That's analogous to the decisions cells have to make every day to survive.

For years, scientists have examined cell behaviors—like the response to cold or hunger—one at a time. And even that they did bit by bit, laboriously hammering out the specific roles of certain molecules. This approach made it difficult or impossible to study the relative contributions of—and the interplay between—genes that share responsibility for cell behaviors, such as the 100 or so genes involved in the control of blood pressure.

Now, computers are allowing scientists to examine many factors involved in cellular behaviors and decisions all at the same time. The field of computational biology blossomed with the advent of high-end computers. For example, sequencing the 3.2 billion base pairs of the human genome, which was completed in 2003, depended on computers advanced enough to tackle the challenge. Now, state-of-the-art equipment and a wealth of biological data from genome projects and other technologies are opening up many new research opportunities in computer analysis and modeling. So, much as microscopes and biochemical techniques revolutionized cell biology centuries ago, computers promise to advance the field just as dramatically in this new century.