Laminin is a large protein located in the extracellular matrix, the intricate network outside of cells that provides structural scaffolding for tissues. The protein acts as a biological adhesive, helping hold different tissue layers together. Its presence is a defining feature of specialized sheets within the matrix that support various cell types. Laminin’s role in maintaining tissue architecture is a subject of extensive study in cell biology.
The Molecular Structure of Laminin
A single laminin molecule is a massive glycoprotein composed of three distinct polypeptide chains: an alpha (α), a beta (β), and a gamma (γ). Multiple versions, or isoforms, of each chain exist. This allows for the formation of at least 15 different types of laminin molecules, each with specialized roles in different tissues. The specific combination of chains determines the properties and name of the resulting laminin, for example, laminin-511.
The three chains twist around one another to form a cross-shaped structure with three short arms and one long arm. The long arm is formed by all three chains coiling together. At the ends of each of the four arms are globular domains, which are compact, spherical protein regions that serve as docking points for other molecules.
Microscopy Techniques for Viewing Laminin
Visualizing laminin requires powerful microscopy to resolve individual molecules or their arrangement within tissues. To see the cross shape of a single molecule, scientists use electron microscopy (EM), and a method called rotary shadowing is particularly effective. In this technique, isolated laminin molecules are sprayed onto a flat surface and then coated with a thin layer of a heavy metal from a low angle. This metal coating creates a “shadow” effect, producing a high-contrast replica that reveals its cruciform structure.
This method allows for precise measurements, showing a human laminin molecule’s long arm can be approximately 97 nm long, while the short arms have differing lengths, such as 34 nm and 42 nm. The images produced by rotary shadowing show the three short arms and one long arm, often with the globular domains visible at their tips. These images were fundamental in establishing the cross-like structure of laminin in the early 1980s.
To understand where laminin is located within living tissue, researchers use immunofluorescence microscopy. This technique relies on antibodies designed to bind very specifically to laminin. Scientists introduce these primary antibodies to a tissue sample, where they attach to the laminin molecules. A secondary antibody, which has a fluorescent dye attached, is then added and binds to the first, “tagging” the laminin with a fluorescent marker.
When the prepared tissue is viewed under a specialized microscope, the laminin’s location is revealed as a glowing pattern. Instead of seeing individual crosses, immunofluorescence shows the collective network of laminin. In tissues like the skin, this appears as a continuous, bright line at the junction between the epidermis and the dermis. This technique visualizes how laminin forms a continuous sheet-like structure.
Laminin’s Function Within the Basement Membrane
The cross-shaped structure of laminin is directly related to its function within the basement membrane, a specialized layer of extracellular matrix. The globular domains at the tips of its short arms bind to other laminin molecules, allowing them to self-assemble into a sheet-like network. This network forms the foundational scaffold of the basement membrane, providing a surface for cells to adhere to and organize.
The basement membrane also functions as a selective barrier. The dense network of laminin and other proteins, like type IV collagen, regulates the passage of molecules between tissue compartments. For example, in the kidney, the laminin-rich basement membrane of the glomerulus is a filtration barrier that prevents proteins from leaking from the blood into the urine.
The long arm of the laminin cross contains binding sites for cellular receptors, such as integrins. By binding to these receptors, laminin communicates with the cells attached to it, influencing their migration, differentiation, and survival. These interactions are important for guiding cells during development and wound healing. This structure allows laminin to bind to itself, other matrix components, and cells, securing tissue architecture.