The peripheral neuroimmune reflex arc illustrates how immune cells can simultaneously respond to both motor and sensory nerves but also transmit signals to

Doctoral position in Medical Science Project title: Advancing Immunotherapy: Enhancing NK Cell Recognition of Cancer The Department of

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.