Niki Baccile, Archan Vyas, Ramanujam Ramanujam, Daniel Hermida-Merino, Ingo Hoffmann, Lionel Porcar, Atul N Parikh ACS Nano 19, 32629-32642 (2025)
Bolaamphiphilesamphiphilic molecules with polar groups at each of the two ends of a hydrophobic tail with pH-sensitive spontaneous molecular curvatures, endow membranes of extremophiles with an exquisite balance between stability (or robustness) and adaptability (or plasticity). But how the presence (or real-time insertion) of bolaamphiphiles influences lamellar lipid membranes is poorly understood. Using a combination of time-resolved confocal fluorescence microscopy, in situ small-angle X-ray and neutron scattering (SAXS and SANS), and neutron spin echo (NSE) measurements, we monitor here the pH-dependent interactions of nanoscopic vesicles of a representative bolaamphiphilea glucolipid consisting of a single glucose headgroup and a C18:1 (oleyl) fatty acid tail (G-C18:1)with the membranes of an essentially cylindrical fluid-phase phospholipid (dioleoylphosphatidylcholine, DOPC). We found that the two mesophases interact spontaneously at all pH values, producing large-scale morphological remodeling. Under neutral and acidic conditions, when the bolaamphiphile assumes a cylindrical shape, vesicles fuse with one another, producing invaginations, inner tubulation, and vesicle-in-vesicle aggregates. Under basic pH, by contrast, when the carboxylic acid is deprotonated and the molecule is inverted-conical in shape, the bolaamphiphile causes phospholipid membranes to undergo poration, budding, and vesiculation. This pH-dependent environmentally sensitive membrane remodeling without the disruption of the essential bilayer motif illustrates how local molecular-level packing perturbations can translate into global system-level morphological changes, enabling membranes to acquire environmental sensitivity and real-time adaptability. These results support the notion that molecular fluxeswhich add (or remove) amphiphilic molecules to biological membranescan endow de novo functionalities (e.g., pH sensitivity) and influence global morphologies of cell-sized vesicles.
DOI:10.1021/acsnano.5c10120