Department of Biomedical Engineering, University of California Davis, Davis, California.
Department of Biomedical Engineering, University of California Davis, Davis, California.
Biophys J. 2022 Dec 6;121(23):4714-4728. doi: 10.1016/j.bpj.2022.10.016. Epub 2022 Oct 14.
Complex motions of immune cells are an integral part of diapedesis, chemotaxis, phagocytosis, and other vital processes. To better understand how immune cells execute such motions, we present a detailed analysis of phagocytic spreading of human neutrophils on flat surfaces functionalized with different densities of immunoglobulin G (IgG) antibodies. We visualize the cell-substrate contact region at high resolution and without labels using reflection interference contrast microscopy and quantify how the area, shape, and position of the contact region evolves over time. We find that the likelihood of the cell commitment to spreading strongly depends on the surface density of IgG, but the rate at which the substrate-contact area of spreading cells increases does not. Validated by a theoretical companion study, our results resolve controversial notions about the mechanisms controlling cell spreading, establishing that active forces generated by the cytoskeleton rather than cell-substrate adhesion primarily drive cellular protrusion. Adhesion, on the other hand, aids phagocytic spreading by regulating the cell commitment to spreading, the maximum cell-substrate contact area, and the directional movement of the contact region.
免疫细胞的复杂运动是细胞出芽、趋化、吞噬和其他重要过程的一个组成部分。为了更好地理解免疫细胞如何执行这些运动，我们对人中性粒细胞在不同密度免疫球蛋白 G（IgG）抗体功能化的平面上的吞噬扩展进行了详细分析。我们使用反射干涉对比显微镜以高分辨率和无标记的方式可视化细胞-基底接触区域，并定量分析接触区域的面积、形状和位置随时间的演变。我们发现细胞扩展的可能性强烈取决于 IgG 的表面密度，但扩展细胞的基底接触面积增加的速度则不然。通过一项理论性的配套研究进行验证，我们的结果解决了有关控制细胞扩展机制的争议性概念，确定了由细胞骨架产生的主动力而非细胞-基底黏附主要驱动细胞突起。另一方面，黏附通过调节细胞扩展的倾向、细胞-基底最大接触面积以及接触区域的定向运动来辅助吞噬扩展。
