Cell Adhesion Mechanisms in Endothelial Biology

Endothelial cells line the interior surface of blood vessels, forming a dynamic barrier that regulates fluid exchange, immune cell trafficking and vascular homeostasis. Cell adhesion mechanisms in these cells are orchestrated by specialised receptors—including cadherins at adherens junctions, selectins and integrins for leukocyte interactions, and immunoglobulin-superfamily members such as PECAM-1 (CD31). These adhesion molecules engage in homophilic and heterophilic binding, organise cytoskeletal linkages and initiate intracellular signalling cascades. Conformational changes, phosphorylation events and local metabolic shifts fine-tune adhesion strength and barrier permeability in response to shear stress, inflammatory mediators or angiogenic cues. Dysregulation of these processes contributes to vascular leak, atherogenesis and tumour neovascularisation. Recent advances have combined metabolic profiling, high-resolution structural biology and molecular imaging to reveal how endothelial junctions disassemble and re-assemble, how adhesion receptors cluster under physiological flow and how cleaved receptor epitopes can serve as in vivo markers of inflammation. A comprehensive understanding of these interconnected adhesion networks is essential for the development of therapies that stabilise vascular barriers and modulate leukocyte extravasation.

Research from Nature Portfolio

Recent studies have revealed that engagement of the CD31 receptor on endothelial cells triggers a rapid shift towards glycolysis, fuelling the re-annealing of intercellular junctions after acute inflammatory disruption. This metabolic reprogramming is orchestrated through Src-phosphatase activation and downstream Akt-mediated transcriptional events that restore barrier integrity. A separate investigation resolved the crystal structures of the first two immunoglobulin-like domains of PECAM-1, delineating the hydrophobic and hydrophilic contacts that drive trans-homophilic dimerisation. These structural insights have clarified how specific domain interfaces support stable cell–cell adhesion under physiological shear forces.

Cell Adhesion Mechanisms in Endothelial Biology publication trend

The graph below shows the total number of articles in cell adhesion mechanisms in endothelial biology across all publications each year (not limited to Nature Index journals).

Technical terms

PECAM-1 (CD31): A cell-surface adhesion molecule of the immunoglobulin superfamily that mediates homophilic and heterophilic interactions at endothelial junctions.

Homophilic adhesion: Binding between identical adhesion receptors on neighbouring cells, critical for junctional stability.

Heterophilic adhesion: Interaction between different receptor types or between receptors and extracellular ligands such as glycosaminoglycans.

Glycolytic reprogramming: The shift of cellular energy metabolism towards glycolysis to rapidly generate ATP for processes such as junction re-annealing.

Immunoglobulin-like domain: A protein fold found in many adhesion molecules, comprising two β-sheet layers that mediate receptor–receptor interactions.

References

1. Preservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming. Nature Communications (2020).
2. Structural Basis for Human PECAM-1-Mediated Trans-homophilic Cell Adhesion. Scientific Reports (2016).
3. Influence of PECAM‐1 ligand interactions on PECAM‐1‐dependent cell motility and filopodia extension. Physiological Reports (2016).
4. Regulation of Endothelial Cell Barrier Function by Antibody-driven Affinity Modulation of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1)*. Journal of Biological Chemistry (2014).
5. Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Homophilic Adhesion Is Mediated by Immunoglobulin-like Domains 1 and 2 and Depends on the Cytoplasmic Domain and the Level of Surface Expression*. Journal of Biological Chemistry (1996).
6. Cleaved CD31 as a target for in vivo molecular imaging of inflammation. Scientific Reports (2019).