Islam Md Mydul, Gaska Ignas, Oshinowo Oluwamayokun, Otumala Adiya, Shekhar Shashank, Au Yong Nicholas, Myers David R
Departments of Physics, Cell Biology and Biochemistry, Emory University, Atlanta, Georgia 30322, USA.
APL Bioeng. 2024 Aug 9;8(3):036109. doi: 10.1063/5.0213761. eCollection 2024 Sep.
Pericytes line the microvasculature throughout the body and play a key role in regulating blood flow by constricting and dilating vessels. However, the biophysical mechanisms through which pericytes transduce microenvironmental chemical and mechanical cues to mediate vessel diameter, thereby impacting oxygen and nutrient delivery, remain largely unknown. This knowledge gap is clinically relevant as numerous diseases are associated with the aberrant contraction of pericytes, which are unusually susceptible to injury. Here, we report the development of a high-throughput hydrogel-based pericyte contraction cytometer that quantifies single-cell contraction forces from murine and human pericytes in different microvascular microenvironments and in the presence of competing vasoconstricting and vasodilating stimuli. We further show that murine pericyte survival in hypoxia is mediated by the mechanical microenvironment and that, paradoxically, pre-treating pericytes to reduce contraction increases hypoxic cell death. Moreover, using the contraction cytometer as a drug-screening tool, we found that cofilin-1 could be applied extracellularly to release murine pericytes from hypoxia-induced contractile and, therefore, may represent a novel approach for mitigating the long-lasting decrease in blood flow that occurs after hypoxic injury.
周细胞遍布全身的微血管，通过收缩和舒张血管在调节血流方面发挥关键作用。然而，周细胞将微环境化学和机械信号转导以介导血管直径从而影响氧气和营养物质输送的生物物理机制，在很大程度上仍不清楚。这一知识空白具有临床相关性，因为许多疾病都与周细胞的异常收缩有关，而周细胞异常容易受到损伤。在这里，我们报告了一种基于水凝胶的高通量周细胞收缩细胞仪的开发，该细胞仪可在不同的微血管微环境中以及在存在竞争性血管收缩和舒张刺激的情况下，量化来自小鼠和人类周细胞的单细胞收缩力。我们进一步表明，缺氧条件下小鼠周细胞的存活由机械微环境介导，而且矛盾的是，预处理周细胞以减少收缩会增加缺氧细胞死亡。此外，使用收缩细胞仪作为药物筛选工具，我们发现丝切蛋白-1可以在细胞外应用，以解除小鼠周细胞的缺氧诱导收缩，因此，这可能代表了一种减轻缺氧损伤后发生的长期血流减少的新方法。
