Understanding the phase behavior and microscopic diffusion mechanism of cationic vesicles is crucial for controlled-release kinetics in gene/DNA transfection. Here, we report our findings on the structure, phase behavior, and microscopic dynamics of a vesicle based on a cationic double-chained surfactant, dihexadecyldimethylammonium bromide (DHDAB), which is a promising candidate for a nonviral gene/DNA carrier. Small-angle neutron-scattering measurements reveal that DHDAB aggregates are in the form of unilamellar vesicles. Calorimetric studies show a strong thermal hysteresis in the heating and cooling cycles following different pathways. Two first-order transitions are observed at 303 and 318 K in the heating cycle. Fourier transform infrared spectroscopy reveals that the first transition (at 303 K) is associated with a polymorphic (solid-solid) transition from coagel to an intermediate crystalline (IC) phase, and subsequently the second transition (at 318 K) is an order-disorder transition from IC to the fluid phase. Interestingly, it is found that in the cooling cycle, the fluid phase directly transforms back into the coagel phase without passing through the IC phase. This is also confirmed by an elastic fixed window scan (EFWS) using incoherent neutron scattering. The phase behavior of DHDAB is in strong contrast to that of its longer-chain counterpart, dioctadecyldimethylammonium bromide (DODAB), where the intermediate gel phase was observed during the cooling cycle. Moreover, no polymorphic transition was observed in the heating cycle of DODAB, in which the coagel phase directly converts to the fluid phase. These sharply contrasting phase behaviors for DHDAB and DODAB suggest the strong dependence of membrane phase behavior to the alkyl chain length. EFWS measurements reveal that the phase transitions observed in the DHDAB membrane are associated with strong changes in the DHDAB dynamics. The changes in conformational entropy of DHDAB molecules estimated from EFWS confirm that the coagel-fluid and IC-fluid phase transitions are accompanied by strong changes in the conformations of the alkyl chains. The microscopic dynamics of DHDAB molecules in each of these phases is investigated by employing quasielastic neutron-scattering (QENS). In the ordered phases (coagel and IC), only localized internal dynamics of the DHDAB is observed in the QENS spectra. However, in the fluid phase, the presence of a long-range lateral diffusion is detected in addition to the localized internal dynamics of the alkyl chain. The lateral motion is found to follow Fickian diffusion. The internal dynamics of DHDAB depends on the phase state of the bilayer. In the ordered phase, the internal dynamics is described by a fractional uniaxial rotational diffusion model. However, in the fluid phase, where alkyl tails are disordered with significant gauche defects, the internal dynamics is described using localized translation within confined spheres. This study highlights the rich phase behavior of the DHDAB membrane and the surfactant dynamics across these phases.

• Received 7 January 2022
• Accepted 24 June 2022

DOI:https://doi.org/10.1103/PhysRevMaterials.6.075602