Extracellular matrix and cell-surface glycocalyx (ECM/Glycocalyx)

The extracellular matrix (ECM) and cell-surface glycocalyx represent the complex structural and functional environment surrounding cells, providing both physical support and biochemical signaling [1.1.2, 1.4.3]. The ECM is a non-cellular network of fibrous proteins, such as collagen and elastin, and polysaccharides like hyaluronan that regulate tissue architecture and cell behavior [1.4.1, 1.4.5]. The glycocalyx is a carbohydrate-rich layer, primarily composed of proteoglycans and glycoproteins, that coats the surface of cells, particularly vascular endothelial cells [1.2.1]. In the vasculature, the glycocalyx acts as a critical permeability barrier and mechanotransducer, sensing shear stress to regulate nitric oxide production [1.3.2, 1.3.5]. In pathological states such as cancer, fibrosis, and sepsis, these structures undergo significant remodeling or degradation, contributing to disease progression and organ dysfunction [1.2.5, 1.4.4]. ECM remodeling in tumors can create a physical barrier to drug delivery and promote metastasis, while glycocalyx shedding in sepsis leads to vascular leakage and inflammation [1.2.4, 1.4.4]. Therapeutic interventions target this environment by either degrading excessive ECM components to improve drug delivery or by restoring the protective glycocalyx layer to maintain vascular integrity [1.3.1, 1.4.2]. Drugs like hyaluronidase and collagenase are used to break down pathological matrix, whereas agents like sulodexide aim to replenish the endothelial surface layer [1.3.3, 1.4.1].

Other names

ECMGlycocalyxPericellular matrixEndothelial glycocalyxExtracellular environmentSurface layer of endothelium

Therapeutic strategies targeting the extracellular matrix and glycocalyx involve the enzymatic degradation of pathological matrix components (e.g., hyaluronan or collagen) to reduce tissue stiffness and improve drug penetration, or the pharmacological restoration of the glycocalyx (e.g., via glycosaminoglycan precursors or protective agents) to maintain the vascular barrier and reduce inflammation [1.3.1, 1.4.1, 1.4.2].