Morphological Changes of Kinetically Trapped Tubular Vesicles Driven by the Production of Synthetic Phospholipids in a Vesicular Membrane Ibuki Ishii, 1 Yuka Ominato, 1 Akane Karasawa, 1 Tatsuya Takahashi, 1 Muneyuki Matsuo, 2,3 Kentaro Suzuki,* 1 and Tadashi Sugawara* 1 1 Department of Chemistry, Faculty of Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan 2 Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro, Tokyo 153-8902, Japan 3 Department of Life and Coordination-Complex Molecular Science, Biomolecular Functions, Institute for Molecular Science, Myodaiji, Okazaki,Aichi 444-8585, Japan E-mail: suzuken@kanagawa-u.ac.jp (K. Suzuki), sugawara-t@kanagawa-u.ac.jp (T. Sugawara) A tubulation of giant vesicles (GVs) composed of zwitterionic phospholipids was induced by the addition of the precursor of the phospholipid. The generated tubular GVs can be regarded as a kinetically-trapped structure because it was converted to more stable spherical GVs by heating through the one-way deformation. Such a morphologicalinterconversion is the rst example to be rationalized by the concept of the thermodynamically and kinetically controlled formation of molecular self-assemblies. Keywords: Giant vesicle | Morphological change | Kinetically trapped structure It isoften observed that a crystal structure of ablock shape is generated inaslow cooling process as a thermally stable crystalline form if an equilibrium between a crystallization of constituent molecules onto the surface of a growing crystal and adissolution from the surface is achieved. On the other hand, a thin needle crystalis formed as a kinetically trapped product in a rapid crystallization with no equilibrium between these two processes. Control of these processes is indispensable for crystal engineering 1 or for regulating polymorphism to express physical properties or specific functions. 2 Asimilar phenomenon is observed in the case of giant molecules e.g., fullerenes and carbon nanotubes derived from a covalent bond formation between carbon atoms. 3 Recently, vesicles, which are self-assembled closed struc- tures of amphiphiles in water, have drawn considerable attention as molecular capsules for enzymatic reactions, 4,5 drug delivery systems (DDS), 6 and compartments for model protocells. 7,8 Control of morphologies e.g., tubulation and budding deforma- tions of giant vesicles (GVs), which is dened as a vesiclewith adiameter larger than 1 ¯m, is important not only from the standpoint of membrane dynamics but also from expressing their functions as above mentioned. 911 These deformations are mainly caused by external physical stimuli, 10,12 such as changes in the osmotic pressure, 13 temperature, 14 electric eld, 15 mag- netic eld 16 and mechanicalforce from biochemical material, 17 and the morphological changes have been successfully ration- alized in terms of the area-difference elasticity (ADE) model theory. 18 However, these morphological changes are not accom- panied by the growth of GVs because even if membrane lipids are supplied to an exterior water phase containing pre-existing GVs, added lipids predominantly form new GVs, not dissolving into the pre-existing GVs. Recently, we have proposed a different way to induce morphological changes of the pre- existing GVs as a resultof the increase in the number of membrane lipids within a GV by adding a precursor of the membrane lipid (Figure 1a). 1922 Thistime we focused on phospholipids with a head group of a phosphocholine-type because the hydrophilic head groups of major phospholipids of living cells are zwitterionic e.g., 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Those phospholipids are characterized by an extremely low critical aggregate concentration (cac). 23 To examine the mor- phological changes in GVs constituted by synthesized phos- pholipids, we prepared artificial zwitterionic phospholipids (Figure 1b, a detailed description of the synthesis is provided in the Supporting Information): 24,25 V PC (D), 1,2-di(10-(4-for- mylphenoxy)decanoyl)-sn-glycero-3-phosphocholine, that bears a phosphocholine group as a hydrophilic head, while the termini of the dual hydrophobic tails bear a benzaldehyde group, and C@GV V PC (D): R = V PC (S): R = V PC (D)*: R = V PC (S)*: R = C@GV + nE C E V PC -GV C C C C Precursor (V PC *) V PC * V PC (a) (b) Morphological Change n = 2 n = 1 Figure 1. (a) Schematic illustration of morphological changes of GV, induced by internal chemical stimuli. (b) Scheme of hydrolysis precursor V PC * to yield membrane lipidV PC in the vesicular membrane containing the lipophilic acid catalyst C. CL-190260 Received: March 29, 2019 | Accepted: May 16, 2019 | Web Released: June 4, 2019 932 | Chem. Lett. 2019, 48, 932935 | doi:10.1246/cl.190260 © 2019 The Chemical Society of Japan