Exploring intermolecular interactions in the presence of biomolecules that dictate director configurations of liquid crystals (LCs) enables new techniques for optically probing complex biological phenomena and realizing new classes of sensors and actuators. However, the design of a new approach by probing direct protein-LC interactions (in aqueous media) that can mimic chemico-biological interactions at the cellular level remains elusive. Here, we present a simple method to produce biocompatible LC droplets through poly(l-lysine) (PLL)-LC interactions in situ for reporting the presence of cells and monitoring the real-time interaction of cells with their environments that are mediated by topological defects in those droplets. In addition, responsive PLL droplets have been found to be useful as a template for reporting Annexin V-phosphatidylserine interactions, providing a simple measure of the harmful effect on cell health.