Microtubule
Based on Wikipedia: Microtubule
The Tiny Tubes That Pull You Apart (To Keep You Alive)
Every time a cell in your body divides, it faces a logistical nightmare. It must duplicate its entire genetic library—three billion base pairs of DNA, packed into forty-six chromosomes—and then physically separate those copies into two new cells. Get this wrong, and you get cancer. Get it very wrong, and you die.
The machinery that solves this problem is breathtakingly elegant: hollow tubes, each about twenty-five nanometers wide, that grow and shrink with stunning precision, grabbing chromosomes and hauling them to opposite sides of the cell. These are microtubules, and they're the reason you exist as a coherent organism rather than a chaotic soup of cells.
But microtubules do far more than split cells. They form the structural beams that give cells their shape. They serve as highways for molecular cargo. They build the whip-like tails that let sperm swim and the hair-like projections that clear mucus from your lungs. And remarkably, the poison that interferes with these tiny tubes—colchicine, extracted from autumn crocus flowers—has been used to treat gout for three thousand years, long before anyone knew cells existed.
Building a Tube from Proteins
To understand microtubules, you need to think small. Really small.
A microtubule is about twenty-five nanometers across. For perspective: if you enlarged a microtubule to the width of a garden hose, a human hair would be roughly the diameter of a subway tunnel. These structures operate at a scale where the random jostling of molecules—Brownian motion—is a constant force, and where the distinction between "solid" and "liquid" starts to blur.
The building blocks are proteins called tubulins. Specifically, two nearly identical proteins: alpha-tubulin and beta-tubulin. These two proteins grab onto each other to form a paired unit called a dimer (from the Greek for "two parts"). Each tubulin protein weighs about fifty kilodaltons—a kilodalton being the standard unit for measuring molecular weight, roughly the mass of a single hydrogen atom multiplied by a thousand.
Here's where it gets interesting. These alpha-beta dimers don't just float around randomly. They stack end-to-end like Lego bricks, always with beta connecting to alpha, forming long chains called protofilaments. Then, typically thirteen of these protofilaments line up side by side and curl around to form a hollow cylinder.
Why hollow? The interior space—the lumen—isn't empty decoration. It provides a channel that certain proteins can travel through, and it makes the tube surprisingly strong for its weight. Think of it like the structural principle behind bamboo or bicycle frames: hollow tubes resist bending forces remarkably well.
A Tale of Two Ends
Every microtubule has a built-in sense of direction, and this polarity is everything.
Because the alpha-beta dimers always stack the same way—beta touching alpha touching beta touching alpha—one end of the tube exposes only beta-tubulin subunits while the other end exposes only alpha-tubulin subunits. Scientists call these the plus end and the minus end, respectively. The names don't refer to electrical charge; they indicate which end grows faster.
The plus end is the action end. It's where new dimers are constantly being added, extending the tube out into the cell like a growing vine. The minus end is typically anchored—held in place by specialized structures that serve as microtubule organizing centers. The most famous of these is the centrosome, a small organelle that sits near the nucleus in animal cells and acts as the hub from which microtubules radiate outward like spokes from a wheel.
This arrangement means microtubules aren't just static scaffolding. They're dynamic highways with a clear direction: cargo moves toward the plus end or toward the minus end, depending on which molecular motor is doing the hauling.
The Search and Capture Dance
In 1986, two scientists named Marc Kirschner and Tim Mitchison proposed a beautiful idea that transformed our understanding of how cells work.
They suggested that microtubules are constantly exploring the interior of the cell, growing outward from the centrosome, probing into the cytoplasm like tentacles searching for something. Most of the time, these growing tubes are unstable. They extend for a while, then suddenly collapse, shrinking back toward the centrosome. This cycle of growth and catastrophic shrinkage happens every five to ten minutes.
But when a growing microtubule tip encounters something important—a chromosome that needs to be moved, a specific location where cargo needs to be delivered—it can be "captured" and stabilized. These captured microtubules stop their frantic growth-and-collapse cycle and become stable highways that can last for hours.
This is the "search and capture" model, and it's elegantly simple. Rather than requiring the cell to precisely engineer where each microtubule goes, the cell simply lets microtubules grow randomly and then stabilizes the ones that happen to find useful targets. It's like searching for something in a dark room by extending your arms in all directions, then holding still when you touch what you're looking for.
The Chemistry of Collapse
What makes microtubules so dramatically unstable? The answer involves a molecular energy currency called guanosine triphosphate, or GTP.
Each tubulin dimer arrives at the growing end of a microtubule carrying two GTP molecules—one bound to the alpha subunit, one bound to the beta subunit. The GTP on alpha stays put, serving a structural role. But the GTP on beta gets hydrolyzed—split apart—shortly after the dimer joins the tube, converting to guanosine diphosphate, or GDP.
This hydrolysis is the key to the whole dynamic system.
GDP-tubulin doesn't like being part of a microtubule. The dimer changes shape slightly when its GTP becomes GDP, creating internal strain in the tube wall. But as long as the very tip of the microtubule still has fresh GTP-tubulin dimers—a "GTP cap"—the whole structure holds together.
The moment that cap disappears—when hydrolysis finally catches up to the growing tip—everything changes. Without GTP-tubulin at the end to hold things in place, the strained GDP-tubulin subunits begin peeling away. The tube doesn't just stop growing; it rapidly disassembles, protofilaments curling outward like a banana peel, dimers flying off into the cytoplasm.
Scientists call this sudden collapse a "catastrophe." It's not a value judgment; it's a technical term for the switch from growth to shrinkage. The reverse event—when a shrinking microtubule suddenly starts growing again—is called a "rescue."
Highways for Molecular Cargo
A tube is only as useful as what travels through or along it.
Microtubules serve as tracks for molecular motors—proteins that literally walk along the tube surface, carrying cargo from one place to another inside the cell. The two main families of these motors are kinesin and dynein, and they walk in opposite directions.
Kinesin generally walks toward the plus end—outward, toward the cell periphery. Dynein walks toward the minus end—inward, toward the centrosome and nucleus. Together, they create a two-way transportation system.
What do they carry? Almost everything that needs to move inside a cell. Mitochondria, the cell's power plants. Vesicles containing proteins destined for secretion. Messenger RNA molecules carrying genetic instructions from the nucleus to the protein-building machinery. Even entire organelles like the endoplasmic reticulum and Golgi apparatus are organized and positioned by motor proteins walking along microtubule tracks.
The walking mechanism itself is remarkable. A kinesin molecule has two "feet" (technically called motor domains) that take alternating steps along the microtubule surface, each step powered by the hydrolysis of adenosine triphosphate, or ATP. The step size is about eight nanometers—exactly the spacing between tubulin dimers along the tube. It's as if the microtubule has built-in ladder rungs, and the motor proteins are evolved to climb them.
The Spindle: Microtubules' Starring Role
When a cell divides, microtubules take center stage in the most dramatic performance in cell biology.
First, the centrosome duplicates. Now there are two microtubule-organizing centers, and they migrate to opposite sides of the cell. From each centrosome, microtubules begin extending, searching the space between them.
Meanwhile, the chromosomes—already duplicated and consisting of two identical copies called sister chromatids, joined at a pinched waist called the centromere—have condensed into visible rods. At each centromere sits a protein complex called the kinetochore, a molecular landing pad specifically designed to capture microtubule tips.
This is search and capture at its most critical. Microtubules from one centrosome must find and attach to one kinetochore, while microtubules from the opposite centrosome must attach to the kinetochore on the other side of the same chromosome. Get this wrong, and the chromosome copies won't separate properly.
Once all chromosomes are properly attached—a process the cell checks carefully before proceeding—the sister chromatids release each other. The microtubules then shorten, literally pulling the chromosomes toward opposite ends of the cell. The mechanism involves both motor proteins walking along the microtubules and the microtubules themselves depolymerizing at the kinetochore attachment point, reeling in the chromosomes like a fishing line being wound onto a reel.
This entire structure—the two centrosomes, the radiating microtubules, the attached chromosomes—is called the mitotic spindle. It's the apparatus that ensures each daughter cell gets exactly one copy of each chromosome. When it fails, the consequences range from cell death to cancer.
Beyond the Spindle: Cilia and Flagella
Microtubules also build the cell's external moving parts.
Cilia are hair-like projections that extend from many cell types. In your respiratory tract, they beat in coordinated waves to push mucus (and the trapped dust and bacteria it contains) up toward your throat. In your fallopian tubes, they help move eggs toward the uterus. In your brain's ventricles, they circulate cerebrospinal fluid.
Flagella are longer versions of the same basic structure—most famously, they form the tails that propel sperm cells.
Inside both cilia and flagella, you'll find microtubules arranged in a characteristic pattern: nine pairs of fused microtubules forming a ring around the perimeter, often with two single microtubules running up the center. This "nine plus two" arrangement is ancient, appearing in organisms from single-celled algae to humans. It's one of the most conserved structures in all of biology.
The movement comes from dynein motors attached between adjacent microtubule pairs. When these motors activate, they try to slide the pairs past each other. But because the microtubules are anchored at the base of the cilium, this sliding force gets converted into bending. The coordinated activation and deactivation of dyneins along the length of the cilium produces the characteristic whip-like beat.
Ancient Observers, Modern Understanding
Antonie van Leeuwenhoek first saw cells moving under his primitive microscope in 1677. He watched sperm swimming, bacteria tumbling, and single-celled organisms gliding through pond water. He was seeing microtubule-powered motion, though he had no framework to understand it.
Two centuries later, improved microscopes revealed that flagella and cilia contained fibrous internal structures. But it wasn't until the twentieth century—with electron microscopes capable of resolving structures smaller than the wavelength of visible light—that scientists could actually see microtubules as distinct tubes.
The biochemical understanding came even later. The ability to isolate tubulin proteins and watch them polymerize in a test tube allowed researchers to discover the GTP cap mechanism, the phenomenon of dynamic instability, and the roles of various associated proteins.
Today, scientists study microtubule motors by attaching fluorescent tags to purified components and watching them move under microscopes. They can see individual kinesin molecules taking their eight-nanometer steps. They can track microtubules growing and shrinking in real time. The invisible molecular machinery that van Leeuwenhoek could only infer from watching cells swim is now directly visible.
Bacterial Cousins
For decades, scientists thought microtubules were exclusively a eukaryotic invention—one of the key features distinguishing cells with nuclei (like ours) from bacteria and archaea.
That changed with the discovery that some bacteria in the genus Prosthecobacter have their own versions of tubulin and can build their own microtubule-like structures. These bacterial tubulins, called BtubA and BtubB, are clearly related to their eukaryotic cousins, but they assemble into simpler tubes with only five protofilaments instead of thirteen.
Even more recently, researchers found an actin-like protein in the soil bacterium Bacillus thuringiensis (famous as the source of the "Bt" genes used in genetically modified crops) that forms tiny tubes called nanotubules. These aren't quite microtubules—they're made of a different protein—but they perform similar functions in the bacterial cell, helping to sort DNA during cell division.
These discoveries suggest that the basic principle of building hollow tubes from protein subunits, then using them for structural support and chromosome segregation, is even more ancient than the origin of complex cells. It may be a fundamental solution to universal problems of cellular architecture.
The Modifications That Matter
Not all microtubules are created equal, even within a single cell.
Long-lived, stable microtubules accumulate chemical modifications on their tubulin subunits—small changes added by enzymes that recognize and bind to microtubules. These modifications include removing the terminal amino acid from alpha-tubulin (detyrosination), adding chains of glutamate molecules (polyglutamylation), and adding chains of glycine (polyglycylation).
The modifications happen slowly, which is why they mark only the stable microtubules—the ones that have been around long enough for the enzymes to do their work. Freshly assembled, rapidly turning over microtubules don't have time to accumulate these marks.
Why does this matter? The modifications change how motor proteins interact with the microtubule surface. Modified tubulins are like road signs, telling molecular cargo "this is a stable, established route" versus "this is a temporary exploratory path." Cells use this system to direct traffic, sending certain cargoes preferentially along the modified microtubules that lead to specific destinations like the front edge of a migrating cell.
When the microtubule eventually depolymerizes, soluble enzymes in the cytoplasm rapidly remove these modifications from the free tubulin dimers, resetting them for incorporation into new tubes.
The Poison Connection
This brings us back to colchicine, the ancient gout remedy.
Colchicine binds to tubulin dimers and prevents them from polymerizing into microtubules. At high doses, this is catastrophic for dividing cells—without functional microtubules, the mitotic spindle can't form, and cell division fails. This is why colchicine and related compounds (like the chemotherapy drugs vincristine and vinblastine, derived from the Madagascar periwinkle) can kill cancer cells.
At lower doses, colchicine's effects are more subtle. It reduces the ability of white blood cells called neutrophils to migrate toward sites of inflammation. Since gout attacks involve neutrophils swarming into joints and releasing inflammatory compounds, dampening their mobility provides relief—even though the underlying cause (uric acid crystals) remains.
For three thousand years, healers knew that autumn crocus extract helped gout without understanding why. Now we know they were manipulating one of the most fundamental systems in cell biology: the dynamic assembly and function of microtubules.
What Makes a Cell a Cell
Microtubules reveal something profound about life at the cellular level: it's not static. A cell isn't a tiny machine with fixed gears and permanent walls. It's more like a city that constantly rebuilds itself, tearing down old infrastructure and constructing new routes in response to changing needs.
The microtubule cytoskeleton—along with its partners, the actin microfilaments and intermediate filaments—provides the dynamic architecture that makes this possible. These protein assemblies grow, shrink, bundle, separate, and reorganize on timescales of minutes to hours, allowing cells to change shape, move, divide, and respond to their environment.
That dynamism comes at a cost in energy (all that GTP and ATP being hydrolyzed) and in complexity (hundreds of proteins regulating assembly, disassembly, and motor function). But it's what allows a single fertilized egg to become the trillions of specialized cells in an adult human body, each arranged in the right place and connected to its neighbors in the right way.
The next time you think about what makes you you, consider the hollow tubes. Twenty-five nanometers wide, constantly growing and collapsing, pulling your chromosomes apart and carrying cargo through your cells. They're doing it right now, in every cell of your body, as they have been every moment of your life.