Yang Ruiguo, Song Bo, Sun Zhiyong, Lai King Wai Chiu, Fung Carmen Kar Man, Patterson Kevin C, Seiffert-Sinha Kristina, Sinha Animesh A, Xi Ning
Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI, 48824, USA.
Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong.
Nanomedicine. 2015 Jan;11(1):137-45. doi: 10.1016/j.nano.2014.08.008. Epub 2014 Sep 6.
We present the nanosurgery on the cytoskeleton of live cells using AFM based nanorobotics to achieve adhesiolysis and mimic the effect of pathophysiological modulation of intercellular adhesion. Nanosurgery successfully severs the intermediate filament bundles and disrupts cell-cell adhesion similar to the desmosomal protein disassembly in autoimmune disease, or the cationic modulation of desmosome formation. Our nanomechanical analysis revealed that adhesion loss results in a decrease in cellular stiffness in both cases of biochemical modulation of the desmosome junctions and mechanical disruption of intercellular adhesion, supporting the notion that intercellular adhesion through intermediate filaments anchors the cell structure as focal adhesion does and that intermediate filaments are integral components in cell mechanical integrity. The surgical process could potentially help reveal the mechanism of autoimmune pathology-induced cell-cell adhesion loss as well as its related pathways that lead to cell apoptosis.
我们展示了使用基于原子力显微镜的纳米机器人对活细胞的细胞骨架进行纳米手术,以实现粘连松解,并模拟细胞间粘附的病理生理调节作用。纳米手术成功地切断了中间丝束,并破坏了细胞间粘附,类似于自身免疫性疾病中桥粒蛋白的分解,或桥粒形成的阳离子调节。我们的纳米力学分析表明,在桥粒连接的生化调节和细胞间粘附的机械破坏这两种情况下,粘附丧失都会导致细胞硬度降低,这支持了这样一种观点,即通过中间丝的细胞间粘附像粘着斑一样锚定细胞结构,并且中间丝是细胞机械完整性的重要组成部分。该手术过程可能有助于揭示自身免疫病理诱导的细胞间粘附丧失的机制及其导致细胞凋亡的相关途径。