Polydiacetylene liposomes have useful potential in biosensor research. To investigate the role of the headgroup in the colorimetric transition, a series of amino acid-derivatized 10,12-pentacosadyanoic acid lipids have been synthesized. The UV-polymerized liposomes undergo an irreversible color change from blue to red in response to a change of specific solution pH. In this system, the color change appears to be due to charge-induced headgroup rearrangement which perturbs the conjugated backbone assembly. Considering the reduced degree of freedom for lipid molecules in polymeric liposomes, a rigid, staggered conformational change in polydiacetylene conjugation is suggested as a likely mechanism for the colorimetric transition.