Proteoglycans are heavily glycosylated proteins, meaning they are proteins decorated with sugar chains. These complex macromolecules are a component of the extracellular matrix (ECM), the substance that exists between cells. They function as the scaffolding and super sponges of our tissues. Proteoglycans provide structural integrity, hydration, and help direct a wide range of cellular behaviors.
The Building Blocks of Proteoglycans
A proteoglycan has two main parts: a central “core protein” and one or more attached sugar chains. Inside the cell, long, unbranched carbohydrate chains called glycosaminoglycans (GAGs) are added to this core protein. These GAG chains are the defining feature of a proteoglycan and can comprise up to 95% of its total weight.
GAG chains are polymers built from repeating disaccharide units, which consist of an amino sugar and a uronic acid. The presence of sulfate and uronic acid groups gives these chains a strong negative charge under physiological conditions. This negative charge is central to their function.
Several major types of GAGs exist, each with different structures and distributions in the body, including chondroitin sulfate in cartilage, dermatan sulfate in skin, and heparan sulfate on cell surfaces. A single core protein can have anywhere from one GAG chain, like decorin, to over 100, as seen in aggrecan. This modular construction allows for a vast diversity of proteoglycan structures, each tailored to a specific location and function.
Role in Tissue Structure and Hydration
The primary physical role of proteoglycans is maintaining tissue architecture and hydration. The high density of negative charges along their GAG chains attracts positively charged ions like sodium. This accumulation of ions then draws large quantities of water into the extracellular matrix through osmosis, forming a hydrated, gel-like substance.
This water-trapping ability gives tissues their resistance to compressive forces. When a tissue is compressed, water is squeezed out of the matrix, but repulsion between the negative GAG chains prevents collapse. Once the force is removed, water is rapidly drawn back in, allowing the tissue to rebound. This creates a cushioning effect in tissues subjected to mechanical stress.
Articular cartilage, the tissue covering the ends of bones in joints, is a prime example. Cartilage is largely composed of the proteoglycan aggrecan, which combines with collagen to form a resilient, shock-absorbing matrix. Aggrecan provides the gel-like properties and resistance to deformation that allow joints to move smoothly. Without this hydration, cartilage would lose its volume and cushioning ability.
Similarly, the dermis layer of the skin owes its firmness and volume to proteoglycans like versican. These molecules maintain the skin’s hydration, contributing to its plump and supple appearance. The ability of proteoglycans to bind and organize water is an aspect of the mechanical properties of many connective tissues.
Influence on Cellular Communication
Beyond their structural duties, proteoglycans actively regulate cellular communication. Those on the cell surface and in the extracellular matrix act as docking stations for signaling molecules like growth factors and cytokines.
Signaling molecules must bind to cell surface receptors to trigger a response. Proteoglycans, especially those with heparan sulfate chains, capture these molecules from the environment. By binding a growth factor, a proteoglycan can present it to its receptor, facilitating the signal. This concentrates signaling molecules near the cell surface, making cellular responses more efficient.
This binding also serves a protective function. Signaling molecules are vulnerable to degradation by enzymes in the extracellular space. When bound to a proteoglycan, they are shielded from these enzymes, which extends their functional lifespan and creates a reservoir of signals for the cell.
By immobilizing signaling molecules, proteoglycans help establish concentration gradients. These gradients guide developmental processes like cell migration during tissue formation and wound healing. Through these interactions, proteoglycans at the cell-matrix interface act as gatekeepers, modulating the flow of information that cells receive and influencing their behavior.
Connection to Aging and Disease
Changes in the amount or structure of proteoglycans are linked to the functional decline of tissues in aging and disease. The consequences are evident in conditions affecting cartilage and skin, such as osteoarthritis. This degenerative joint disease is a clear example of what happens when proteoglycan balance is lost.
In a healthy joint, there is a steady turnover of aggrecan in the cartilage. In osteoarthritis, however, the activity of enzymes that break down proteoglycans increases, accelerating aggrecan degradation. As aggrecan is lost, the cartilage loses its ability to hold water. This makes it less resilient and more susceptible to damage from mechanical stress, resulting in joint pain and loss of mobility.
A similar process occurs in the skin during aging. A reduction of proteoglycans in the dermis decreases tissue hydration and organization. This loss of the skin’s hydrated cushion contributes to a loss of firmness and the formation of wrinkles. The decline can be accelerated by factors like sun exposure.
The inability to properly break down and recycle proteoglycans causes a group of genetic disorders known as mucopolysaccharidoses. In these conditions, mutations in the enzymes that degrade GAGs lead to their accumulation within cells. This accumulation causes a wide range of severe symptoms.