Intimal stiffening upregulates endothelial cell contractility, disrupting barrier integrity; however, intimal stiffening is non-uniform. The impact of local changes in intimal stiffness on proximal and distal cell–cell interactions is unknown. To investigate the range at which matrix stiffness heterogeneities impact neighboring endothelial cells within a monolayer, we built a micropillar system with adjacent regions of stiff and compliant matrix. The stiffness interface results in an oscillatory pattern of neutrophil transendothelial migration, symmetrical about the interface and well-fit by a sinusoid function. ‘Peaks’ of the sinusoid were found to have increased cellular contractility and decreased barrier function relative to ‘troughs’ of the sinusoid. Pharmacological modulation of contractility was observed to break symmetry, altering the amplitude and wavelength of the sinusoid, indicating that contractility may regulate this effect. This work illuminates a novel biophysical phenomenon of the role of stiffness-mediated cell–matrix interactions on cell–cell interactions at a distance. Additionally, it provides insight into the range at which intimal matrix stiffness heterogeneities will impact endothelial barrier function and potentially contribute to atherogenesis.

内膜硬化上调内皮细胞收缩性，破坏屏障完整性；然而，内膜硬化是不均匀的。内膜硬度的局部变化对近端和远端细胞间相互作用的影响尚不清楚。为了研究基质刚度异质性影响单层内相邻内皮细胞的范围，我们构建了一个具有刚性和柔顺基质相邻区域的微柱系统。刚度界面导致中性粒细胞跨内皮迁移的振荡模式，关于界面对称并且通过正弦函数良好拟合。研究发现，相对于正弦波的“波谷”，正弦波的“波峰”具有增加的细胞收缩性和降低的屏障功能。观察到收缩性的药理调节打破了对称性，改变了正弦曲线的幅度和波长，表明收缩性可以调节这种效应。这项工作阐明了一种新的生物物理现象，即刚度介导的细胞-基质相互作用对远距离细胞-细胞相互作用的作用。此外，它还可以深入了解内膜基质硬度异质性影响内皮屏障功能并可能导致动脉粥样硬化形成的范围。