8. The extracellular matrix (ECM) is a complex combination of secreted proteins that is involved in holding cells and tissues together. The components of ECM form a network by binding to each other and communicate with cells by binding to adhesion receptors on the cell surface. ECM comprises mainly two classes of macromolecules, proteoglycans and very high molecular weight large proteins.
   Which one of the following statements regarding ECM constituents is INCORRECT?
   (1) Proteoglycans are a subset of secreted or cell surface-attached glycoproteins
   containing covalently linked specialized polysaccharide chains called glycosamino- glycans (GAGs).
   (2) GAGs are long branched polymers of specific repeating disaccharides of sialic acid and glucose or galactose.
   (3) Major types of GAGs present in ECM are heparan sulphate, chondroitin sulphate, dermatan sulphate, keratan sulphate and hyaluronan.
   (4) Major types of large proteins present in ECM are collagen, laminin, elastin and fibronectin.

Introduction: What Is the Extracellular Matrix?

The extracellular matrix (ECM) is a complex, dynamic network of secreted molecules that provides structural support, environmental cues, and organization for cells and tissues. Its primary components—proteoglycans and high molecular weight proteins—interact with each other, forming a meshwork through which cells receive signals and anchorage.​

Proteoglycans and Glycosaminoglycans (GAGs) in ECM

Proteoglycans are glycoproteins with covalently attached glycosaminoglycan (GAG) chains, contributing significantly to the ECM’s hydration and physical properties. GAGs, themselves, are unbranched, negatively charged polysaccharides made up of repeating disaccharide units—composed of an amino sugar and a uronic acid—such as N-acetylglucosamine and glucuronic acid. This structure enables GAGs to interact extensively with proteins and ions, vital for cell adhesion and migration.​

Identifying the Incorrect Statement

Let’s evaluate the detailed steps in the prompt:

• Statement 1: Correct—Proteoglycans are a subset of glycoproteins with covalently linked GAGs.​

• Statement 2: INCORRECT—GAGs are not branched polymers, nor are they composed of sialic acid and glucose or galactose, but are linear chains with repeating disaccharides made from amino sugars (often N-acetylglucosamine or N-acetylgalactosamine) and uronic acids.​

• Statement 3: Correct—Major ECM GAGs include heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronan (hyaluronic acid).​

• Statement 4: Correct—Key ECM proteins are collagen, laminin, elastin, and fibronectin; all have critical structural or adhesive functions.​

Table: Statement Analysis on ECM Constituents

The True Structure of GAGs

Glycosaminoglycans are critical ECM molecules, forming the “ground substance” and helping resist compressive forces. They are unbranched, highly negatively charged, and enable ECM hydration and signaling. They do not contain sialic acid as a repeating core, nor do they form branched structures; these properties distinguish them from other polysaccharides.​

Major ECM Proteins and GAGs

• Collagen: Provides tensile strength for tissues.

• Elastin: Grants elasticity and recoil.

• Fibronectin: Facilitates adhesion and wound healing.

• Laminin: Supports cell attachment and tissue organization.

• GAGs: Heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, hyaluronan—each with unique tissue roles.​

Conclusion

• Statement (2) is the only incorrect claim about ECM constituents, as it misrepresents the structure and composition of GAGs by suggesting they are branched and contain sialic acid, when in reality they are linear and made of amino sugar–uronic acid repeating disaccharide units.​

• Understanding proper ECM composition is key to grasping cell communication, tissue integrity, and disease mechan