Interfacial assemblies formed by polymeric amphiphiles at aqueous interfaces of thermotropic liquid crystals (LCs) can trigger multiscale changes in the organization of the LCs in response to recognition events. However, we have a limited understanding of the rules architecture governing the rational design of LC-integrated polymeric amphiphiles. Herein, we report the synthesis of families of amphiphilic polymers that differ in (i) side-chain molecular structure, (ii) polymer architecture, and (iii) copolymer composition. We used this library in experiments to establish structure-property relationships relevant to the design of multifunctional polymers that can amplify and transduce biomolecular recognition events into optically detectable, macroscopic ordering transitions in LCs. We then utilized these structure-property relationships to guide the design of a peptide-polymer amphiphile (PPA) that assembles at the interface of LC droplets. Enzymatic cleavage of PPA-coated LC droplets by thermolysin directly triggered a change in the internal ordering of the LC within the droplets and the scattering of light from the droplets. The results of our study provide important guidance to future designs of triggerable LC systems.