免疫细胞,如巨噬细胞和树突状细胞,可以利用podosomes,机械敏感的富含肌动蛋白的突起,为了产生力量,migrate,并巡逻外来抗原。个体podosome通过周期性的突起和收缩周期(高度振荡)探测其微环境,而集群中多个podosome的振荡以波状方式协调。然而,控制个体振荡和集体波状动力学的机制仍不清楚。这里,通过整合肌动蛋白聚合,肌球蛋白收缩性,肌动蛋白扩散,和机械敏感信号,我们开发了一个化学力学模型,用于集群中的podosome动力学。我们的模型表明,当肌动蛋白聚合驱动的突起和信号相关的肌球蛋白收缩以相似的速率发生时,足细胞体显示振荡生长,而肌动蛋白单体的扩散驱动波浪状协调的足体振荡。我们的理论预测通过不同的药理学处理和微环境刚度对化学机械波的影响得到了验证。我们提出的框架可以阐明在伤口愈合和癌症免疫疗法的背景下,囊体在免疫细胞机械传感中的作用。
Immune cells, such as macrophages and dendritic cells, can utilize
podosomes, mechanosensitive actin-rich protrusions, to generate forces, migrate, and patrol for foreign antigens. Individual
podosomes probe their microenvironment through periodic protrusion and retraction cycles (height oscillations), while oscillations of multiple
podosomes in a cluster are coordinated in a wave-like fashion. However, the mechanisms governing both the individual oscillations and the collective wave-like dynamics remain unclear. Here, by integrating actin polymerization, myosin contractility, actin diffusion, and mechanosensitive signaling, we develop a chemo-mechanical model for podosome dynamics in clusters. Our model reveals that
podosomes show oscillatory growth when actin polymerization-driven protrusion and signaling-associated myosin contraction occur at similar rates, while the diffusion of actin monomers drives wave-like coordination of podosome oscillations. Our theoretical predictions are validated by different pharmacological treatments and the impact of microenvironment stiffness on chemo-mechanical waves. Our proposed framework can shed light on the role of
podosomes in immune cell mechanosensing within the context of wound healing and cancer immunotherapy.