Quantification of low-affinity kinetics between cancer immunity relevant ligands and natural killer cell receptors with a self-induced back-action actuated nanopore electrophoresis (SANE) sensor

George Alexandrakis; Sai Santosh Sasank Peri; Manoj Kumar Subnani; Usman Muhammad Raza; Soroush Ghaffari; Jung Soo Lee; Min Jun Kim; Jon Weidanz

doi:10.1117/12.2569816

20 August 2020 Quantification of low-affinity kinetics between cancer immunity relevant ligands and natural killer cell receptors with a self-induced back-action actuated nanopore electrophoresis (SANE) sensor

George Alexandrakis, Sai Santosh Sasank Peri, Manoj Kumar Subnani, Usman Muhammad Raza, Soroush Ghaffari, Jung Soo Lee, Min Jun Kim, Jon Weidanz

Author Affiliations +

Proceedings Volume 11463, Optical Trapping and Optical Micromanipulation XVII; 1146306 (2020) https://doi.org/10.1117/12.2569816
Event: SPIE Nanoscience + Engineering, 2020, Online Only

Abstract

A plasmonic nanopore sensor enabling detection of bimodal optical and electrical molecular signatures was fabricated and tested for its ability to characterize low affinity ligand-receptor interactions. This plasmonic nanosensor uses a Self- Induced Back-Action (SIBA) mechanism for optical trapping to enable SIBA-Actuated Nanopore Electrophoresis (SANE) sensing through a nanopore located immediately below the optical trap volume. The ligand-receptor model consisted of a Natural Killer (NK) cell inhibitory receptor heterodimer molecule CD94/NKG2A that was synthesized to target a specific peptide-presenting Qa-1^b Qdm ligand. The latter interaction pair was used as a simplified model of lowaffinity interactions between immune cells and peptide-presenting cancer cells that occur during cancer immunotherapy. A cancer-irrelevant GroEL ligand was also targeted by the same receptor in control experiments to test for non-specific interactions. Although the analysis of different pairs of bimodal SANE sensor signatures enabled some level of discrimination between specific and non-specific interactions the separation was not complete, which suggested the need for multi-dimensional data analyses in future work. Nevertheless, the SANE sensor showed ability to quantify the fast dissociation rate (k_off) in this low-affinity model system that was previously shown to be challenging to quantify with commercial technologies. The k_off value of targeted peptide-presenting ligands is known to correlate with the subsequent activation of immune cells in vivo, suggesting the potential utility of the SANE sensor as a screening tool in cancer immunotherapy.

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George Alexandrakis, Sai Santosh Sasank Peri, Manoj Kumar Subnani, Usman Muhammad Raza, Soroush Ghaffari, Jung Soo Lee, Min Jun Kim, and Jon Weidanz "Quantification of low-affinity kinetics between cancer immunity relevant ligands and natural killer cell receptors with a self-induced back-action actuated nanopore electrophoresis (SANE) sensor", Proc. SPIE 11463, Optical Trapping and Optical Micromanipulation XVII, 1146306 (20 August 2020); https://doi.org/10.1117/12.2569816

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