Veena S Manasa, Chen Dixiao, Kumar Akshay, Pratap Rudra, Young Jennifer L, Tijore Ajay
Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
Nano Lett. 2025 Feb 12;25(6):2418-2425. doi: 10.1021/acs.nanolett.4c05858. Epub 2025 Jan 30.
Cancer cells sense and respond to the extracellular environment, with differences in nanoscale ligand spacing affecting their behavior. Emerging reports show that stretch/ultrasound-mediated mechanical forces promote apoptosis (mechanoptosis) by increasing myosin contractility. Since myosin contractility is critical for nanoscale-ligand spacing-regulated cell behavior, we study the effect of ligand spacing on mechanoptosis. Gold nanoparticle arrays were created with 35, 50, and 70 nm spacings and functionalized with cyclic-RGD peptide. Interestingly, the highest level of apoptosis was observed on 50 and 70 nm ligand spacing, where increased myosin contractility and peripheral Piezo1 channel localization causing calcium influx were observed. Perturbing cell-matrix interactions by nanomolar doses of Cilengitide (cyclic RGD pentapeptide) increases mechanoptosis on 35 nm ligand spacing to similar levels observed on 50 and 70 nm. Thus, nanoscale-level changes in binding domains regulate mechanoptosis through cell-matrix mediated mechanotransduction, and the synergistic action of ultrasound and Cilengitide can ultimately be applied to enhance tumor treatment.
癌细胞感知并响应细胞外环境，纳米级配体间距的差异会影响其行为。新出现的报道表明，拉伸/超声介导的机械力通过增加肌球蛋白收缩性来促进细胞凋亡（机械性细胞凋亡）。由于肌球蛋白收缩性对于纳米级配体间距调节的细胞行为至关重要，我们研究了配体间距对机械性细胞凋亡的影响。制备了具有35、50和70纳米间距的金纳米颗粒阵列，并用环RGD肽进行功能化修饰。有趣的是，在50和70纳米的配体间距上观察到了最高水平的细胞凋亡，在这些间距上还观察到肌球蛋白收缩性增加以及外周Piezo1通道定位导致钙内流。用纳摩尔剂量的西仑吉肽（环RGD五肽）干扰细胞与基质的相互作用，可使35纳米配体间距上的机械性细胞凋亡增加到与50和70纳米上观察到的相似水平。因此，结合域的纳米级变化通过细胞-基质介导的机械转导来调节机械性细胞凋亡，超声和西仑吉肽的协同作用最终可用于增强肿瘤治疗。
