Antivesiculation and Complete Unbinding of Tail-Tethered Lipids.

We report the effect of tail-tethering on vesiculation and complete unbinding of bilayered membranes. Amphiphilic molecules of a bolalipid, resembling the tail-tethered molecular structure of archaeal lipids, with two identical zwitterionic phosphatidylcholine headgroups self-assemble into a large flat lamellar membrane, in contrast to the multilamellar vesicles (MLVs) observed in its counterpart, monopolar nontethered zwitterionic lipids. The antivesiculation is confirmed by small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cyro-TEM). With the net charge of zero and higher bending rigidity of the membrane (confirmed by neutron spin echo (NSE) spectroscopy), the current membrane theory would predict that membranes should stack with each other (aka "bind") due to dominant van der Waals attraction, while the outcome of the nonstacking ("unbinding") membrane suggests that the theory needs to include entropic contribution for the nonvesicular structures. This report pioneers an understanding of how the tail-tethering of amphiphiles affects the structure, enabling better control over the final nanoscale morphology.

Water Content in Nanoparticles Determined by Small-Angle Neutron Scattering and Light Scattering.

The amount of water in therapeutic nanoparticles (NPs) is of great importance to the pharmaceutical industry, as water content reflects the volume occupied by the solid components. For example, certain biomolecules, such as mRNA, can undergo conformational change or degradation when exposed to water. Using static light scattering (SLS) and dynamic light scattering (DLS), we estimated the water content of NPs, including extruded liposomes of two different sizes and polystyrene (PS) Latex NPs. In addition, we used small-angle neutron scattering (SANS) to independently access the water content of the samples. The water content of NPs estimated by SLS/DLS was systematically higher than that from SANS. The discrepancy is most likely attributed to the larger radius determined by DLS, in contrast to the SANS-derived radius observed by SANS. However, because of low accessibility to the neutron facilities, we validate the combined SLS/DLS to be a reasonable alternative to SANS for determining the water (or solvent) content of NPs.

DRR1 promotes neuroblastoma cell differentiation by regulating CREB expression.

BACKGROUND: Neuroblastoma is the most common cancer in infants and the most common extracranial solid tumor in childhood. DRR1 was identified to be downregulated in poorly differentiated ganglion cells from neuroblastoma model mice. However, the roles of DRR1 in neuroblastoma remain largely unclear. METHODS: The neuroblastoma cells were induced to differentiate, and the expression of DRR1 was detected. The expression of the neuroblastoma cell differentiation markers was analyzed in DRR1 shRNA- or DRR1-expressing vector-treated neuroblastoma cells. The downstream genes of DRR1 were screened with ChIP-seq assay. Finally, TNB1 cells were infected with DRR1 shRNA and CREB expressing vector containing lentivirus, and the expression of the cell differentiation markers, cell cycle distribution and tumor growth were analyzed. RESULTS: The expression of DRR1 was increased in differentiated neuroblastoma cells, and downregulation of DRR1 expression inhibited the differentiation of neuroblastoma cells. Further experiments indicated that CREB is a candidate downstream gene of DRR1, and it mediates neuroblastoma cell differentiation. Moreover, overexpression of CREB rescued the effect of DRR1 shRNA on cell differentiation, cell cycle distribution and tumor growth in neuroblastoma. CONCLUSIONS: DRR1-CREB axis modulates the differentiation of neuroblastoma cells and is associated with the outcome of neuroblastoma patients. IMPACT: DRR1 is involved in regulation of the differentiation of neuroblastoma. Binding with actin is essential for DRR1 to regulate neuroblastoma cell differentiation. CREB is a candidate downstream gene of DRR1 in regulating of the differentiation of neuroblastoma.

Identification of the glutamine synthetase (GS) gene family in four wheat species and functional analysis of Ta4D.GSe in Arabidopsis thaliana.

Drought stress can negatively impact crop yield and quality. Improving wheat yields under drought stress is a major objective of agronomic research. Glutamine synthetase (GS) is a key enzyme of nitrogen metabolism that is critical to plant growth and development in abiotic stress response. However, to date, no systemic characterization of the GS genes has yet been conducted in wheat and its close relatives. We identified a total of 15 GS genes in Triticum aestivum (2n = 6x = 42; AABBDD), as well as 9 GS genes in Triticum dicoccoides (2n = 4x = 28; AABB), 6 in Aegilops tauschii (2n = 2x = 14; DD), and 5 in Triticum urartu (2n = 2x = 14; AA). The 35 GSs were further clustered into five lineages according to the phylogenetic tree. Synteny analysis revealed that the three subgenomes in bread wheat retained extensive synteny between bread wheat and its three relative species. We identified three up-regulated TaGSs (Ta4A.GSe, Ta4B.GSe, and Ta4D.GSe) from transcriptome data after drought and salt stress. Ta4D.GSe was subsequently used for further functional studies, and its subcellular localization were determined in Arabidopsis protoplasts. Its overexpression in Arabidopsis enhanced drought tolerance by increasing the ability of scavenging of reactive oxygen species (ROS) and osmotic adjustment. We identified GS gene family in four wheat species and performed comparative analyses of their relationships, chromosome locations, conserved motif, gene structure, and synteny. The subcellular localization of Ta4D.GSe was detected and its drought tolerance function was demonstrated. Taken together, these findings provide insight into the potential functional roles of the GS genes in abiotic stress tolerance. KEY MESSAGE: This report clearly shows detailed characterization of GS gene family in four wheat species and demonstrates that Ta4D.GSe plays an important role in enhancing drought tolerance by improving the scavenging of ROS and osmotic adjustment ability in Arabidopsis.

Head on Comparison of Self- and Nano-assemblies of Gamma Peptide Nucleic Acid Amphiphiles.

Peptide nucleic acids (PNAs) are nucleic acid analogs with superior hybridization properties and enzymatic stability than deoxyribonucleic acid (DNA). In addition to gene targeting applications, PNAs have garnered significant attention as bio-polymer due to the Watson-Crick -based molecular recognition and flexibility of synthesis. Here, we engineered PNA amphiphiles using chemically modified gamma PNA (8 mer in length) containing hydrophilic diethylene glycol units at the gamma position and covalently conjugated lauric acid (C12) as a hydrophobic moiety. Gamma PNA (γPNA) amphiphiles self-assemble into spherical vesicles. Further, we formulate nano-assemblies using the amphiphilic γPNA as a polymer via ethanol injection-based protocols. We perform comprehensive head-on comparison of the physicochemical and cellular uptake properties of PNA derived self- and nano-assemblies. Small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) analysis reveal ellipsoidal morphology of γPNA nano-assemblies that results in superior cellular delivery compate to the spherical self-assembly. Next, we compare the functional activities of γPNA self-and nano-assemblies in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis-based assays. Overall, we establish that γPNA amphiphile is a functionally active bio-polymer to formulate nano-assemblies for a wide range of biomedical applications.

Chronic sleep fragmentation enhances habenula cholinergic neural activity.

Sleep is essential to emotional health. Sleep disturbance, particularly REM sleep disturbance, profoundly impacts emotion regulation, but the underlying neural mechanisms remain elusive. Here we show that chronic REM sleep disturbance, achieved in mice by chronic sleep fragmentation (SF), enhanced neural activity in the medial habenula (mHb), a brain region increasingly implicated in negative affect. Specifically, after a 5-day SF procedure that selectively fragmented REM sleep, cholinergic output neurons (ChNs) in the mHb exhibited increased spontaneous firing rate and enhanced firing regularity in brain slices. The SF-induced firing changes remained intact upon inhibition of glutamate, GABA, acetylcholine, and histamine receptors, suggesting cell-autonomous mechanisms independent of synaptic transmissions. Moreover, the SF-induced hyperactivity was not because of enhanced intrinsic membrane excitability, but was accompanied by depolarized resting membrane potential in mHb ChNs. Furthermore, inhibition of TASK-3 (KCNK9) channels, a subtype of two-pore domain K+ channels, mimicked the SF effects by increasing the firing rate and regularity, as well as depolarizing the resting membrane potential in mHb ChNs in control-sleep mice. These effects of TASK-3 inhibition were absent in SF mice, suggesting reduced TASK-3 activity following SF. By contrast, inhibition of small-conductance Ca2+-activated K+ (SK) channels did not produce similar effects. Thus, SF compromised TASK-3 function in mHb ChNs, which likely led to depolarized resting membrane potential and increased spontaneous firing. These results not only demonstrate that selective REM sleep disturbance leads to hyperactivity of mHb ChNs, but also identify a key molecular substrate through which REM sleep disturbance may alter affect regulation.

Outer membrane vesicles (OMVs) enabled bio-applications: A critical review.

Outer membrane vesicles (OMVs) are nanoscale spherical vesicles released from Gram-negative bacteria. The lipid bilayer membrane structure of OMVs consists of similar components as bacterial membrane and thus has attracted more and more attention in exploiting OMVs' bio-applications. Although the endotoxic lipopolysaccharide on natural OMVs may impose potential limits on their clinical applications, genetic modification can reduce their endotoxicity and decorate OMVs with multiple functional proteins. These genetically engineered OMVs have been employed in various fields including vaccination, drug delivery, cancer therapy, bioimaging, biosensing, and enzyme carrier. This review will first briefly introduce the background of OMVs followed by recent advances in functionalization and various applications of engineered OMVs with an emphasis on the working principles and their performance, and then discuss about the future trends of OMVs in biomedical applications.

Changes Experienced by Low-Concentration Lipid Bicelles as a Function of Temperature.

Differential scanning calorimetry (DSC) of dipalmitoyl phosphatidylcholine (DPPC), dihexanoyl phosphatidylcholine, and dipalmitoyl phosphatidylglycerol bicelles reveals two endothermic peaks. Based on analysis of small angle neutron scattering and small angle X-ray scattering data, the two DSC peaks are associated with the melting of DPPC and a change in bicellar morphology─namely, either bicelle-to-spherical vesicle or oblate-to-spherical vesicle. The reversibility of the two structural transformations was examined by DSC and found to be consistent with the corresponding small angle scattering data. However, the peak that is not associated with the melting of DPPC does not correspond to any structural transformation for bicelles containing distearoyl phosphatidylethanolamine conjugated with polyethylene glycol. Based on complementary experimental data, we conclude that membrane flexibility, lipid miscibility, and differential solubility between the long- and short-chain lipids in water are important parameters controlling the reversibility of morphologies experienced by the bicelles.

Self-assembled materials from cellulose nanocrystals conjugated with a thermotropic liquid crystalline moiety.

Manipulating molecular and supramolecular interactions within cellulose nanocrystals (CNCs) to introduce different levels of assemblies combined with multiple functionalities is required for the development of degradable smart materials from renewable resources. To attain hierarchical structures and stimuli-responsive properties, a new class of liquid crystalline cellulosic hybrid materials is synthesized. Herein, main-chain rigid-rod-like oxidized cellulose (CNC-COOH) is prepared from a Cellulose Whatman filter paper (Cellulose W.P.) by acid hydrolysis and oxidized using 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). Thermotropic LC molecule, 4-cyano-4'-hydroxybiphenyl with a 12-methylene spacer (CB12-OH) is grafted onto the carboxylic acid group of CNC-COOH via Steglich esterification. The liquid crystalline functionalized CNCs cellulose nanocrystals (CNC-COO-CB12) are readily soluble in DMSO and ionic liquids. The extent of functionalization and structure of CNC-COO-CB12 are confirmed by solution-state 1H NMR and supported by other characterization techniques. We investigate the interplay of liquid crystalline orientational order of CNCs and cyanobiphenyl (CB12), and the supramolecular hydrogen bonding of CNCs within CNC-COO-CB12 and compare it with CNC-COOH. The introduction of thermotropic CB12 side chains onto rigid-rod CNCs shows the exclusive formation of smectic mesophases from the assemblies of CB12 with the absence of the cholesteric mesophase typically observed from CNC-COOH as verified by temperature-controlled SAXS (T-SAXS). This is further verified by UV-visible and SEM studies that show CNC-COO-CB12 forms smectic domains while CNC-COOH forms a visible light reflecting cholesteric mesophase in dried films. Thus, the interplay of liquid crystalline order of CNCs and CB12 and supramolecular hydrogen bonding of CNCs results in ordered, smectic-mesostructured CNCs for use in stimuli-responsive functional materials.

A Comprehensive Landscape for Fibril Association Behaviors Encoded Synergistically by Saccharides and Peptides.

Nature provides us a panorama of fibrils with tremendous structural polymorphism from molecular building blocks to hierarchical association behaviors. Despite recent achievements in creating artificial systems with individual building blocks through self-assembly, molecularly encoding the relationship from model building blocks to fibril association, resulting in controlled macroscopic properties, has remained an elusive goal. In this paper, by employing a designed set of glycopeptide building blocks and combining experimental and computational tools, we report a library of controlled fibril polymorphism with elucidation from molecular packing to fibril association and the related macroscopic properties. The growth of the fibril either axially or radially with right- or left-handed twisting is determined by the subtle trade-off of oligosaccharide and oligopeptide components. Meanwhile, visible evidence for the association process of double-strand fibrils has been experimentally and theoretically proposed. Finally the fibril polymorphs demonstrated significant different macroscopic properties on hydrogel formation and cellular migration control.

Down-regulated in renal cell carcinoma 1 (DRR1) regulates axon outgrowth during hippocampal neuron development.

Down-regulated in renal cell carcinoma 1 (DRR1), a unique stress-induced protein, is highly expressed in the nervous system. This study investigated the roles of DRR1 in the brain by examining its expression pattern at different developmental stages of a rat brain and in cultured primary hippocampal neurons. High expression of DRR1 was observed in all developmental stages of a rat brain and cultured primary hippocampal neurons. We then focused on the role of DRR1 in promoting neurite outgrowth during the early stage of hippocampal neuron development. Results showed that down-regulation of DRR1 suppressed axon outgrowth. Mass spectrometry analysis revealed that tropomodulin-2 (Tmod2) is a novel binding partner of DRR1. Our results showed that both DRR1 and Tmod2 mediate axon formation during the early stage of hippocampal neuron development. Suppression of TMOD2 expression rescued the abnormal axon outgrowth induced by DRR1 knockdown during the early stage of hippocampal neuron development.

Aggregation-Enhanced Photoluminescence and Photoacoustics of Atomically Precise Gold Nanoclusters in Lipid Nanodiscs (NANO2).

The authors designed a structurally stable nano-in-nano (NANO2) system highly capable of bioimaging via an aggregation-enhanced NIR excited emission and photoacoustic response achieved based on atomically precise gold nanoclusters protected by linear thiolated ligands [Au25(SC n H2n+1)18, n = 4-16] encapsulated in discoidal phospholipid bicelles through a one-pot synthesis. The detailed morphological characterization of NANO2 is conducted using cryogenic transmission electron microscopy, small/wide angle X-ray scattering with the support of molecular dynamics simulations, providing information on the location of Au nanoclusters in NANO2. The photoluminescence observed for NANO2 is 20-60 times more intense than that of the free Au nanoclusters, with both excitation and emission wavelengths in the near-infrared range, and the photoacoustic signal is more than tripled. The authors attribute this newly discovered aggregation-enhanced photoluminescence and photoacoustic signals to the restriction of intramolecular motion of the clusters' ligands. With the advantages of biocompatibility and high cellular uptake, NANO2 is potentially applicable for both in vitro and in vivo imaging, as the authors demonstrate with NIR excited emission from in vitro A549 human lung and the KB human cervical cancer cells.

Structural Engineering in the Self-Assembly of Amphiphilic Block Copolymers with Reactive Additives: Micelles, Vesicles, and Beyond.

Control of polymer assemblies in solution is of great importance to determine the properties and applications of these polymer nanostructures. We report a novel co-self-assembly strategy to control the self-assembly outcomes of a micelle-forming amphiphilic block copolymer (BCP) of poly(ethylene oxide) (PEO) and poly[3-(trimethoxysilyl)propyl methacrylate] (PTMSPMA), PEO114-b-PTMSPMA228. With a reactive and hydrophobic additive tetraethyl orthosilicate (TEOS), the assembly nanostructures of PEO114-b-PTMSPMA228 are tunable. The swelling of the PTMSPMA block by hydrophobic TEOS increases the hydrophobic-to-hydrophilic ratio that enables a continuous morphological evolution from spherical micelles to vesicles and eventually to large compound vesicles. TEOS that co-hydrolyzes with the PTMSPMA block can further stabilize and fix these hybrid nanostructures. With high TEOS concentrations, these polymer assemblies can be further converted through thermal annealing into unique silica nanomaterials, including nanospheres, hollow nanoparticles with dual shells, and mesoporous silica frameworks that cannot be synthesized through conventional syntheses otherwise.

Cd0.5Zn0.5S/CoWO4 Nanohybrids with a Twinning Homojunction and an Interfacial S-Scheme Heterojunction for Efficient Visible-Light-Induced Photocatalytic CO2 Reduction.

The construction of a phase junction photocatalyst can significantly enhance the photocatalytic performance with high selectivity for CO2 reduction. In this study, an S-scheme junction Cd0.5Zn0.5S/CoWO4 semiconductor with the coupling of a twin crystal Cd0.5Zn0.5S homojunction and CoWO4 was designed through a hydrothermal method, which could convert CO2 to CO with high efficiency under visible-light illumination. Cd0.5Zn0.5S-10%CoWO4 exhibited the optimal performance and its CO yield and selectivity were up to 318.68 µmol·g-1 and 95.90%, respectively, which were 4.54 and 1.62 times higher than that of twin crystal Cd0.5Zn0.5S. Moreover, the Cd0.5Zn0.5S homojunction with a zinc-blende and wurtzite phase and the S-scheme phase junction of Cd0.5Zn0.5S/CoWO4 enhanced the property of CO2 adsorption and accelerated the detachment of photogenerated carriers. The combination of photogenerated holes in Cd0.5Zn0.5S and the electrons of CoWO4 can retain the reduction sites to improve photocatalytic performance. This study provides a neoteric concept and reference for the construction of the S-scheme phase junction.

Metallo-Helicoid with Double Rims: Polymerization Followed by Folding by Intramolecular Coordination.

In this study, we established a feasible strategy to construct a new type of metallo-polymer with helicoidal structure through the combination of covalent polymerization and intramolecular coordination-driven self-assembly. In the design, a tetratopic monomer (M) was prepared with two terminal alkynes in the outer rim for polymerization, and two terpyridines (TPYs) in the inner rim for subsequent folding by selective intramolecular coordination. Then, the linear covalent polymer (P) was synthesized by polymerization of M via Glaser-Hay homocoupling reaction. Finally, intramolecular coordination interactions between TPYs and Zn(II) folded the backbone of P into a right- or left-handed metallo-helicoid (H) with double rims. Owing to multiple positive charges on the inner rim of helicoid, double-stranded DNA molecules (dsDNA) could interact with H through electrostatic interactions. Remarkably, dsDNA allowed exclusive formation of H with right handedness by means of chiral induction.

DNA-Mediated Step-Growth Polymerization of Bottlebrush Macromonomers.

Herein, we report the DNA-mediated self-assembly of bivalent bottlebrush polymers, a process akin to the step-growth polymerization of small molecule monomers. In these "condensation reactions", the polymer serves as a steric guide to limit DNA hybridization in a fixed direction, while the DNA serves as a functional group equivalent, connecting complementary brushes to form well-defined, one-dimensional nanostructures. The polymerization was studied using spectroscopy, microscopy, and scattering techniques and was modeled numerically. The model made predictions of the degree of polymerization and size distribution of the assembled products, and suggested the potential for branching at hybridization junctions, all of which were confirmed experimentally. This study serves as a theoretical basis for the polymer-assembly approach which has the potential to open up new possibilities for suprapolymers with controlled architecture, macromonomer sequence, and end-group functionalities.

Bicelles Rich in both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins.

How the distinctive lipid composition of mammalian plasma membranes impacts membrane protein structure is largely unexplored, partly because of the dearth of isotropic model membrane systems that contain abundant sphingolipids and cholesterol. This gap is addressed by showing that sphingomyelin and cholesterol-rich (SCOR) lipid mixtures with phosphatidylcholine can be cosolubilized by n-dodecyl-ß-melibioside to form bicelles. Small-angle X-ray and neutron scattering, as well as cryo-electron microscopy, demonstrate that these assemblies are stable over a wide range of conditions and exhibit the bilayered-disc morphology of ideal bicelles even at low lipid-to-detergent mole ratios. SCOR bicelles are shown to be compatible with a wide array of experimental techniques, as applied to the transmembrane human amyloid precursor C99 protein in this medium. These studies reveal an equilibrium between low-order oligomer structures that differ significantly from previous experimental structures of C99, providing an example of how ordered membranes alter membrane protein structure.

Correlation of the hierarchical structure with rheological behavior of polypseudorotaxane gel composed of pluronic and ß-cyclodextrin.

We have identified the hierarchical (primary, secondary, tertiary and quaternary) structures of a polypseudorotaxane (PPR) gel composed of the Pluronic F108 and ß-cyclodextrin system to be ß-cyclodextrin crystalline, lamellar sheets, lamellar stacks and "grains", respectively. The correlation between the rheological properties and the proposed structures under shear flows was rationalized. Alignment of lamellar stacks and reorganization of grain boundaries under shear flows were investigated by rheo-SANS, small angle X-ray scattering and small-angle light scattering. The relaxation of highly aligned lamellar stacks is slow (>2 h) after flow cessation compared to that of the regrouped grains (a few minutes). The main contribution to thixotropic behavior is likely from the faster relaxation of the reorganized grains containing highly oriented lamellar stacks. The comprehensive understanding of structure-function relationship of the PPR gel will facilitate the rational design for its applications.

Long non-coding RNA LINC01503 promotes the progression of hepatocellular carcinoma via activating MAPK/ERK pathway.

Background: Increasing evidence has implicated that lncRNAs (long non-coding RNAs) play significant roles in carcinogenesis and progression of HCC (hepatocellular carcinoma). LINC01503 is a new lncRNA related to several tumors. Nonetheless, its role in HCC still remains unclear. Methods: The expression levels of LINC01503 in HCC, normal liver tissues as well as HCC cell lines were evaluated by TCGA (The Cancer Genome Atlas) and real-time PCR assay, respectively. The relationship between LINC01503 levels and the prognosis of patients with HCC was evaluated using Kaplan-Meier survival analysis. Then the potential biological functions and pathways related to LINC01503 were investigated by GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, and GSEA v4.0.1 software was employed. Furthermore, the influence of LINC01503 on the proliferation and apoptosis of HCC cells was confirmed using CCK8 assay, flow cytometry, and clone formation assay in cell experiments. Also the pro-tumor effect of LINC01503 was verified by mice xenograft experiment in vivo. In addition, the functional pathway of LINC01503 was proved by western blot and rescue experiments. Results: LINC01503 was highly expressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage, and poor prognosis of HCC patients. Silencing LINC01503 with shRNA significantly restrained the proliferation of MHCC-97H HCC cells and strengthened the apoptosis, while up-regulation of LINC01503 in Huh7 HCC cells contributed to the contrary effects. Besides, LINC01503 promoted tumor growth of nude mice transplanted with liver cancer cells. Mechanistically, MAPK/ERK signaling pathway was activated by LINC01503, inhibition of which could alleviate the pro-tumor effect of LINC01503, consistent with the forecast of GSEA (Gene Set Enrichment Analysis). Conclusion: LINC01503 is highly expressed in HCC and promotes the progression of HCC via MAPK/ERK pathway, which maybe a new potential biomarker and therapeutic target for HCC.

Chemically Controlled Helical Polymorphism in Protein Tubes by Selective Modulation of Supramolecular Interactions.

Polymorphism has been the subject of investigation across different research disciplines. In biology, polymorphism could be interpreted in such a way that discrete biomacromolecules can adopt diversiform specific conformations/packing arrangement, and this polymorph-dependent property is essential for many biochemical processes. For example, bacterial flagellar filament, composed of flagellin, switches between different supercoiled state allowing the bacteria to swim and tumble. However, in artificial supramolecular systems, it is often challenging to achieve polymorph control and prediction, and in most cases, two or more concomitant polymorphs of similar formation energies coexist. Here, we show that a tetrameric protein with properly oriented binding sites on its surface can arrange into diverse protein tubes with distinct helical parameters by adding specifically designed inducing ligands. We examined several parameters of the ligand that would influence the protein tube formation and found that the flexibility of the ligand linker and the dimerization pose of the ligand complex is critical for the successful production of the tubes and eventually influence the specific helical polymorphs of the formed tubes. A surface lattice accommodation model was further developed to rationalize the geometrical relationship between each helical tube type. Molecular simulation was used to elucidate the interactions between ligands and SBA and molecular basis for polymorphic switching of the protein tubes. Moreover, the kinetics of structural formation was studied and the ligand design was found that can affect the kinetics of the protein polymerization pathway. In short, our designed protein tubes serves as an enlightening system for understanding how a protein polymer composed of a single protein switches among different helical states.