Investigating the effect of nanoscale ligand presentation on mechanical force-induced cancer cell killing
Implementing Organization
Indian Institute of Science
Principal Investigator
Prof. Ajay Tijore
Indian Institute of Science
Project Overview
Cells interact with extracellular matrix (ECM) using integrins, which activate signaling pathways to control cell functions. ECM properties, such as rigidity, topography, protein fiber diameter, and spatial distribution of cell binding domains, affect integrin-mediated signaling pathways. The size range of these properties is in the order of tens of nanometers. To study cell-ECM interactions at the nanoscale level, it is crucial to consider the nanoscale spacing between binding domains present on ECM. Cells recognize nanometer-scale changes and respond by altering focal adhesions, stress fiber formation, and traction force generation to activate appropriate signaling pathways. Limited studies have shown the effect of nanoscale ligand presentation on cancer cell behavior, especially survival. Cancer cells are vulnerable to stretch/ultrasound-mediated mechanical forces and undergo apoptosis when subjected to physiologically relevant mechanical forces. This study aims to address this gap by examining the effect of nanoscale ligand presentation on cancer cell survival under ultrasound-mediated mechanical stresses, focusing on breast and oral cancer types. The study will fabricate, functionalize, and characterize an AuNP platform mimicking in vivo nanoscale ligand spacing, examine cancer cell activities, and determine the correlation between ligand nanospacing and cancer cell behavior, particularly apoptosis. Optimization of ultrasound-mediated mechanical forces will be done to further promote cancer cell apoptosis on the AuNP platform.