Foldable polymers with alternating single strand deoxyribonucleic acid (ssDNA) and planar conjugated organic perylene tetracarboxylic diimide units were found to self-organize into various folded nanostructures. The biological sequence provides highly specific molecular recognition properties while the physical properties of synthetic chromophores offer sensitive fluorescence detection. Such rational designed hybrid foldamers exhibit potential in the detection of polynucleotides. Under strictly controlled laboratory conditions, fluorescence measurements indicate that configuration change due to binding of polynucleotides with one or two mismatched bases can be readily distinguished. Moreover, some folded structures become more ordered as evidenced by pi-stacking in the perylene segments at high temperature. The folding and unfolding processes driven by the molecular interactions of adjacent perylenes were monitored in both aqueous and organic solutions. Heat-promoted folding, or inverse temperature behavior, which originates from positive enthalpy changes, was only observed in water. Finally, these well-defined linear multichromophoric foldamers with a specific sequence of alternating rigid perylene chromophores and flexible ethylene glycol chains was studied by single molecule fluorescence spectroscopy. Monomer showed minor spectral fluctuations compared to trimer and hexamer, which showed unusual and colorful spectral dynamics attributed to a stochastic photoinduced unfolding/folding phenomenon. The rate of switching between different spectral shapes in the spectral trajectories suggests the existence of multiple pathways between the folded and unfolded states. These findings shed light on the design of new thermophiles in protein engineering as well as the construction of macromolecular-based nano-devices with actuator and sensory properties.