Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?

Nonlamellar lipid arrangements, including cubosomes, appear in unhealthy cells, e.g., when they are subject to stress, starvation, or viral infection. The bioactivity of cubosomes-nanoscale particles exhibiting bicontinuous cubic structures-versus more common vesicles is an unexplored area due to lack of suitable model systems. Here, glycodendrimercubosomes (GDCs)-sugar-presenting cubosomes assembled from Janus glycodendrimers by simple injection into buffer-are proposed as mimics of biological cubic membranes. The bicontinuous cubic GDC architecture has been demonstrated by electron tomography. The stability of these GDCs in buffer enabled studies on lectin-dependent agglutination, revealing significant differences compared with the vesicular glycodendrimersome (GDS) counterpart. In particular, GDCs showed an increased activity toward concanavalin A, as well as an increased sensitivity and selectivity toward two variants of banana lectins, a wild-type and a genetically modified variant, which is not exhibited by GDSs. These results suggest that cells may adapt under unhealthy conditions by undergoing a transformation from lamellar to cubic membranes as a method of defense

A supramolecular helix that disregards chirality

The functions of complex crystalline systems derived from supramolecular biological and non-biological assemblies typically emerge from homochiral programmed primary structures via first principles involving secondary, tertiary and quaternary structures. In contrast, heterochiral and racemic compounds yield disordered crystals, amorphous solids or liquids. Here, we report the self-assembly of perylene bisimide derivatives in a supramolecular helix that in turn self-organizes in columnar hexagonal crystalline domains regardless of the enantiomeric purity of the perylene bisimide. We show that both homochiral and racemic perylene bisimide compounds, including a mixture of 21 diastereomers that cannot be deracemized at the molecular level, self-organize to form single-handed helical assemblies with identical single-crystal-like order. We propose that this high crystalline order is generated via a cogwheel mechanism that disregards the chirality of the self-assembling building blocks. We anticipate that this mechanism will facilitate access to previously inaccessible complex crystalline systems from racemic and homochiral building blocks

X-ray diffraction study of dendritic structures self-assembled into supramolecular hollow columnar and cubic phases

Families of dendritic architectures were characterized with the goal of mimicking natural porous structures. The structural and retro-structural analysis combined small and wide angle powder and fiber x-ray diffraction with other experimental techniques. Based on the reconstruction of powder x-ray diffraction amplitudes we developed a general methodology that provides the calculation of various structural parameters of the dendritic structures self-assembled into supramolecular hollow columnar or cubic phases. Applying this methodology we established some general principles that govern the self-assembly mechanism of the dendritic hollow supramolecular structures. Our systematic research provided the tools to master at the Angstrom level the pore size and separation of supramolecular self-assembled hollow dendritic structures, and illustrated some of the advantages of synthetic functional porous materials over the natural ones

Molecular design principles of helical pyramidal chirality self-organized from achiral hexakis(alkyloxy)triphenylene

2,3,6,7,10,11-Hexakis(alkyloxy)triphenylene (HATn) containing n = 4 to 12 carbons in its alkyl groups, are a classic group of discotic molecules self-organizing columnar liquid crystals. The structure of the crystalline assemblies of these discotic molecules were neglected since they were invented 45 years ago. Recently, we discovered that the crystal state of HAT4 consists of a highly ordered 8/1 helical chiral pyramidal 3D self-organization. In this publication we report the structural analysis of all 3D self-organizations of HATn containing n = 4 to 12 carbons in their achiral alkyls. Unexpectedly, the highly ordered 8/1 helical chiral pyramidal crystalline columns assembled from the crown-conformation of HAT4 is encountered also in the crystalline periodic array of HAT5. HAT6 self-organizes a 5/1 helical chiral pyramidal 3D column. HAT7 to HAT10 maintain their crown conformation in their 3D supramolecular pyramidal columns. However, their 3D pyramidal assemblies exhibit a nonhelical criss-cross arrangement. HAT11 and HAT12 self-organize 3D nonhelical columns from criss-cross arrangements of disc-like conformers. The structures of all these 3D helical and nonhelical pyramidal as well as of nonhelical discotic columns were resolved for the first time at the molecular level by reconstruction of their oriented fiber X-ray diffractograms with the help of molecular models. These results demonstrate that a single self-assembling building block can self-organize either helical chiral pyramidal or nonhelical pyramidal or even nonhelical discotic assemblies via two of its constitutional isomers. This outcome prompts essential questions related to the current standing of helical self-organizations. The most important question is, why over the past many years the scientific community explored helical self-organizations derived from long alkyl groups when the ideal alkyls for this process seem to be short? A hypothetic explanation of the findings reported here and of their impact on the field of helical self-organizations is presented

Enhancing conformational flexibility of dendronized triphenylene via diethylene glycol linkers lowers transitions of helical columnar, Frank-Kasper, and quasicrystal phases

A library of triphenylene (Tp) dendronized with self-assembling dendrons via a diethylene glycol linker was synthesized and the corresponding self-organizations were analyzed. They self-organize via a crown conformation in helical columns and spherical helices that produce hexagonal columnar, Frank-Kasper and soft quasicrystal assemblies. The same self-organizations are produced in the absence of the diethylene glycol linker except that the phase transitions and isotropization temperatures occur at lower temperatures in the presence of the linker. The incorporation of the flexible diethylene glycol linker induces also strong π-π stacking in helical columns. Spherical helices are spherical distorted short fragments of helical columns and therefore the same principles determine the thermal stability of the hexagonal columnar and of Frank-Kasper and quasicrystal assemblies except that the length of the supramolecular backbone is much longer in helical columns. A comparison of these systems with side-chain liquid crystals indicates that supramolecular dendrimers are stabilized by extended supramolecular backbone conformations. This result suggests pathways to molecularly engineer phase transitions of supramolecular dendrimers self-organized from crown conformations

Self-Organizable Vesicular Columns Assembled from Polymers Dendronized with Semifluorinated Janus Dendrimers Act As Reverse Thermal Actuators

The synthesis and structural analysis of polymers dendronized with self-assembling Janus dendrimers containing one fluorinated and one hydrogenated dendrons are reported. Janus dendrimers were attached to the polymer backbone both from the hydrogenated and from the fluorinated parts of the Janus dendrimer. Structural analysis of these dendronized polymers and of their precursors by a combination of differential scanning calorimetry, X-ray diffraction experiments on powder and oriented fibers, and electron density maps have demonstrated that in both cases the dendronized polymer consists of a vesicular columnar structure containing fluorinated alkyl groups on its periphery. This vesicular columnar structure is generated by a mechanism that involves the intramolecular assembly of the Janus dendrimers into tapered dendrons followed by the intramolecular self-assembly of the resulting dendronized polymer in a vesicular column. By contrast with conventional polymers dendronized with self-assembling tapered dendrons this new class of dendronized polymers acts as thermal actuators that decrease the length of the supramolecular column when the temperature is increased and therefore, are called reverse thermal actuators. A mechanism for this reversed process was proposed

Losing supramolecular orientational memory via self-organization of a misfolded secondary structure

Supramolecular orientational memory (SOM) provides a route to otherwise inaccessible nanoscale architectures for certain molecules. In these privileged cases, columnar domains organized from self-assembling dendrons undergo reorientation during heating to, and subsequent cooling from, a 3D phase composed of “spheres”, such as a body-centered cubic phase or a Pm[3 with combining macron]n cubic phase, known also as Frank-Kasper A15. The directions of the reoriented columns preserve key interactions from the preceding cubic phase. However, SOM was observed so far in a very limited number of assemblies. The molecular determinants enabling SOM, and its generality, remain poorly understood. Here we report the synthesis and structural and retrostructural analysis of a perylene bisimide (PBI) with two self-assembling benzyl ether dendrons, 3,5-G2-PBI, and compare its assemblies with those of a previously reported PBI, 3,4,5-G2-PBI, which exhibits SOM and has an additional minidendritic building block in its dendrons. The removal of this minidendron in 3,5-G2-PBI eliminates its ability to self-assemble into supramolecular spheres and organize into a cubic phase, thereby precluding 3,5-G2-PBI from exhibiting SOM. This finding demonstrates hierarchical transfer of structural information from primary structure to material function, analogous to the misfolding of proteins into toxic structures such as those implicated in Alzheimer's and Prion diseases. The concepts exemplified here provide new insights into the hierarchical basis for SOM and will aid in the translation of the SOM concept to a broader diversity of soft matter such as block copolymers and surfactants

Conformationally flexible dendronized cyclotetraveratrylenes (CTTV)s self-organize a large diversity of chiral columnar, Frank-Kasper and quasicrystal phases

Primary structure endows the tertiary structure while the tertiary structure determines the function of hierarchical self-organizations. This is a well-established fundamental principle both for biological and non-biological synthetic assemblies. The role of the conformational flexibility-rigidity in this process is less understood. Here we select the conformationally flexible monodisperse tetramer of veratrole, 2,3,7,8,12,13,17,18-octamethoxy-5,10,15,20-tetrahydrotetrabenzo[a,d,g,j]-cyclododecatetraene, known as cyclotetraveratrylene (CTTV) and use it as an apex model to compare with the less flexible corresponding trimer known as cyclotriveratrylenes (CTV) and with the rigid triphenylene (Tp) and 1,3,5-trihydroxybenzene (THB) when dendronized with libraries of self-assembling dendrons and with n-alkyl groups. Unexpectedly, a large diversity of chiral helical assemblies including supramolecular columns assembled from chiral spheres and crowns, 12-fold quasi liquid crystals (QLC), Frank-Kasper A15 (space group Pm3¯n) but not σ phases (space group P42/mnm), and supramolecular orientational memory effect (SOM) were observed in the case of the dendronized CTTV. The more rigid structures at the apex provide thermally more stable helical chiral periodic and quasiperiodic self-organizations with lowed dynamics which may facilitate the freezing of metastable rather than equilibrium structures. Conformational flexibility also changes the structure of the self-organization generated from supramolecular spheres. These experiments indicate that additional studies on the topic of conformational flexibility are desirable