Cephalopods (e.g., squids, octopuses, and cuttlefishes) possess remarkable dynamic camouflage abilities and therefore have emerged as powerful sources of inspiration for the engineering of dynamic optical technologies. Within this context, we have focused on the development of engineered living systems that can emulate the tunable optical characteristics of some squid skin cells. Herein, we expand our ability to controllably incorporate reflectin-based structures within mammalian cells via genetic engineering methods, and demonstrate that such structures can facilitate holotomographic and standard microscopy imaging of the cells. Moreover, we show that the reflectin-based structures within our cells can be reconfigured with a straightforward chemical stimulus, and we quantify the stimulus-induced changes observed for the structures at the single cell level. The reported findings may enable a better understanding of the color- and appearance-changing capabilities of some cephalopod skin cells and could afford opportunities for reflectins as molecular probes in the fields of cell biology and biomedical optics.