Pericytes (PCs) have been reported to contribute to the mechanoregulation of the capillary diameter and blood flow in health and disease. How this is realized remains poorly understood. We designed several models representing basement membrane (BM) in between PCs and endothelial cells (ECs). These models captured a unique protein organization with micron-sized FN patches surrounded by laminin (LM) and allowed to obtain quantitative information on PC morphology and contractility. Using human induced pluripotent stem cell-derived PCs, we could address mechanical aspects of mid-capillary PC behavior in vitro. Our results showed that PCs strongly prefer FN patches over LM for adhesion formation, have an optimal stiffness for spreading in the range of EC rigidity, and react in a non-canonical way with increased traction forces and reduced spreading on other stiffness then the optimal. Our approach opens possibilities to further study PC force regulation under well-controlled conditions.

据报道，周细胞（PC）有助于健康和疾病中毛细血管直径和血流的机械调节。如何实现这一点仍然知之甚少。我们设计了几种代表PC和内皮细胞（EC）之间的基底膜（BM）的模型。这些模型捕获了具有层粘连蛋白（LM）包围的微米级FN补丁的独特蛋白质组织，并获得了有关PC形态和收缩力的定量信息。使用人类诱导的多能干细胞衍生的PC，我们可以解决体外中毛细血管PC行为的机械方面。我们的结果表明，PC相对于LM而言，与LM相比，FN补丁更受青睐，它们具有在EC刚度范围内扩展的最佳刚度，并以非规范的方式反应，从而增加了牵引力，并减小了其他刚度下的最佳扩张。我们的方法为进一步研究在良好控制的条件下PC力调节提供了可能性。