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Mechanobiology of the blood-brain barrier during development, disease and ageing

Simon Konig, Vignesh Jayarajan, Selina Wray, Roger D. Kamm, Emad Moeendarbary

2025Nature Communications43 citationsDOIOpen Access PDF

Abstract

The blood-brain barrier (BBB) preserves brain health through selective permeability, and its disruption is a hallmark of many neurological disorders. Mechanical stimuli such as shear stress and cyclic strain are increasingly recognised to influence BBB integrity and function, while alterations in tissue stiffness and extracellular matrix composition contribute to its breakdown during ageing and disease. Despite its importance, BBB mechanobiology remains underexplored. Here we highlight the central role of mechanics in BBB development, pathology, and ageing, identify key knowledge gaps, and argue that combining innovative BBB model systems with mechanical probing techniques could transform therapeutic strategies targeting brain vascular dysfunction.

Topics & Concepts

MechanobiologyBlood–brain barrierNeuroscienceAgeingExtracellular matrixDiseaseMedicinePathologyBiologyCentral nervous systemCell biologyAnatomyInternal medicineBarrier Structure and Function StudiesDiet and metabolism studiesNeurological Disease Mechanisms and Treatments
Mechanobiology of the blood-brain barrier during development, disease and ageing | Litcius