Cartilage is a specialized connective tissue found throughout the body, notably in joints, the nose, and the ears. This tissue is designed to withstand significant mechanical forces, requiring a unique combination of flexibility and shock absorption. The exceptional mechanical properties of cartilage are derived from its extracellular matrix (ECM), a complex network of fibers and molecules that surrounds the cells. Proteoglycans are a major class of molecules within this ECM, and their function is central to the tissue’s ability to operate under load.
The Molecular Structure of Proteoglycans
Proteoglycans are complex macromolecules defined by a core protein to which one or more long, unbranched carbohydrate chains, known as glycosaminoglycans (GAGs), are covalently attached. The primary proteoglycan in cartilage is Aggrecan, a massive molecule that resembles a bottle brush in its structure. The GAG chains, which can constitute up to 90% of the molecule’s weight, extend perpendicularly from the protein core.
In cartilage Aggrecan, the GAG chains are predominantly chondroitin sulfate and keratan sulfate. The repeating disaccharide units within these GAG chains possess a high density of negatively charged sulfate and carboxylate groups.
These numerous negative charges are fixed within the cartilage matrix, creating a localized high concentration of anions. This fixed charge density is the fundamental structural property that dictates the molecule’s subsequent mechanical function. The mutual electrostatic repulsion between the negative charges on the chains forces the GAGs to adopt a highly extended conformation, occupying a large volume relative to their mass.
Creating the Cartilage Hydrostatic Cushion
The high density of fixed negative charges along the GAG chains makes the proteoglycans highly hydrophilic, meaning they strongly attract water molecules. To maintain electrical neutrality, the negative charges also attract a large number of positively charged ions from the surrounding fluid. This influx of ions increases the solute concentration inside the proteoglycan-rich matrix compared to the fluid outside.
This concentration difference generates a substantial osmotic gradient, which pulls large volumes of water into the extracellular matrix. The tendency of the proteoglycans to draw and hold water creates an internal resistance known as the osmotic swelling pressure. This swelling pressure provides the tissue with its turgidity and its ability to resist deformation.
When a compressive load is applied to the joint, such as during walking or running, the tissue is squeezed, causing water to be temporarily pushed out of the matrix. This movement of fluid forces the GAG chains closer together, which intensifies the electrostatic repulsion between the negative charges and further increases the internal osmotic swelling pressure. The increased pressure then acts as a counter-force, balancing the external load.
This mechanism converts the cartilage matrix into a hydraulic shock absorber, where the bulk of the compressive stress is borne by the pressurized fluid, not the solid components of the tissue. Upon removal of the external load, the inherent osmotic pressure draws the displaced water back into the matrix, restoring the tissue to its original volume. The ability of the proteoglycans to generate this recoverable hydrostatic cushion allows cartilage to sustain decades of mechanical use without failure.
Organizing the Cartilage Matrix
Beyond their role in hydration, proteoglycans perform a structural function by organizing the extracellular matrix into a cohesive, load-bearing network. The Aggrecan molecules do not exist individually; instead, they form massive superstructures called proteoglycan aggregates. This aggregation process is mediated by a long, non-sulfated GAG chain called hyaluronic acid (hyaluronan).
Dozens to over a hundred individual Aggrecan core proteins non-covalently bind along the length of a single hyaluronic acid filament. A small glycoprotein, known as the link protein, stabilizes this association, creating an extremely large, multi-component molecular complex. These Aggrecan-hyaluronan aggregates are too large to diffuse freely through the cartilage matrix.
The enormous Aggrecan aggregates become physically entrapped within the dense, interwoven meshwork of collagen fibers that runs through the cartilage. The collagen network provides the necessary tensile strength to contain the swelling pressure generated by the proteoglycans. This entrapment anchors the Aggrecan in place, preventing the high internal osmotic pressure from simply pushing the molecules out of the tissue.
The organized interplay between the collagen fibers, which restrain expansion, and the Aggrecan aggregates, which generate internal pressure, provides the tissue with its mechanical integrity. The collagen network determines the tissue’s resistance to tension, while the proteoglycans primarily provide resistance to compression.
Proteoglycans and Cartilage Health
The delicate balance maintained by proteoglycans is directly linked to the health and longevity of the joint. In degenerative joint diseases, such as osteoarthritis, the earliest destructive changes often involve the degradation and loss of Aggrecan from the matrix. This loss is primarily caused by the activity of specific enzymes, particularly members of the ADAMTS family.
The enzymatic cleavage of the Aggrecan core protein releases the molecules from their anchoring to the hyaluronic acid chain, allowing them to escape the collagen network. The subsequent loss of these negatively charged molecules reduces the fixed charge density within the matrix, resulting in a proportional reduction in the osmotic swelling pressure.
Without the full complement of proteoglycans to draw in and retain water, the cartilage becomes dehydrated and loses its turgidity and resilience. This loss of the hydrostatic cushion impairs the tissue’s ability to absorb compressive loads, leading to increased stress on the collagen network and the underlying bone. The reduced shock absorption and increased friction accelerate the destructive cycle of joint degeneration.