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Background and Purpose: The effective connectivity of neuronal networks during passive saltatory pneumotactile velocity stimulation to the glabrous hand with different velocities is still unknown. The present study investigated the effectivity connectivity elicited by saltatory pneumotactile velocity arrays placed on the glabrous hand at three velocities (5, 25, and 65 cm/second). Methods: Dynamic causal modeling (DCM) was used on functional MRI data sampled from 20 neurotypical adults. Five brain regions, including the left primary somatosensory (SI) and motor (M1) cortices, bilateral secondary somatosensory (SII) cortices, and right cerebellar lobule VI, were used to build model space. Results: Three velocities (5, 25, and 65 cm/second) of saltatory pneumotactile stimuli were processed in both serial and parallel modes within the sensorimotor networks. The medium velocity of 25 cm/second modulated forward interhemispheric connection from the contralateral SII to the ipsilateral SII. Pneumotactile stimulation at the medium velocity of 25 cm/second also influenced contralateral M1 through contralateral SI. Finally, the right cerebellar lobule VI was involved in the sensorimotor networks. Conclusions: Our DCM results suggest the coexistence of both serial and parallel processing for saltatory pneumotactile velocity stimulation. Significant contralateral M1 modulation promotes the prospect that the passive saltatory pneumotactile velocity arrays can be used to design sensorimotor rehabilitation protocols to activate M1. The effective connectivity from the right cerebellar lobule VI to other cortical regions demonstrates the cerebellum's role in the sensorimotor networks through feedforward and feedback neuronal pathways. [ABSTRACT FROM AUTHOR]

Background and Objectives: Substance use disorder (SUD) includes maladaptive patterns of substance use despite negative consequences. Previous structural neuroimaging studies showed some structural alterations in SUD, but it remains unknown whether these alterations are specifically associated with SUD or common comorbidities. This study attempts to validate the findings of structural differences between SUD, healthy controls (HC), and psychiatric controls (PC). Methods: We used HC (N = 86) matched for demographics, and PC (N = 86) matched for demographics and psychiatric diagnoses to a group of SUD patients (N = 86). We assessed the group differences of subcortical volumes, cortical volumes, thickness, and surface areas between SUD and HC. We then analyzed the group differences between SUD and PC within regions showing differences between SUD and HC. Results: SUD had smaller left nucleus accumbens, right thalamus, right hippocampus, left caudal anterior cingulate cortex (ACC) volume, and larger right caudal ACC volume, and right caudal ACC, right caudal middle frontal gyrus (MFG), and right posterior cingulate cortex (PCC) surface than HC. Increased right caudal ACC volume and right PCC surface in SUD were the only findings when compared with PC. Several areas showed thickness alterations between SUD and HC, but none survived multiple comparisons vs PC. Discussion and Conclusions: Our findings suggest that cingulate structures may be altered in SUD compared with both HC and PC. Scientific Significance: These results are among the first to indicate that some structural alterations may be SUD‐specific, and highlight a cautionary note about using HC in psychiatric biomarker research. (Am J Addict 2021;30:72–79) [ABSTRACT FROM AUTHOR]

The cortical representations of orofacial pneumotactile stimulation involve complex neuronal networks, which are still unknown. This study aims to identify the characteristics of functional connectivity (FC) evoked by three different saltatory velocities over the perioral and buccal surface of the lower face using functional magnetic resonance imaging in twenty neurotypical adults. Our results showed a velocity of 25 cm/s evoked stronger connection strength between the right dorsolateral prefrontal cortex and the right thalamus than a velocity of 5 cm/s. The decreased FC between the right secondary somatosensory cortex and right posterior parietal cortex for 5-cm/s velocity versus all three velocities delivered simultaneously ("All ON") and the increased FC between the right thalamus and bilateral secondary somatosensory cortex for 65 cm/s vs "All ON" indicated that the right secondary somatosensory cortex might play a role in the orofacial tactile perception of velocity. Our results have also shown different patterns of FC for each seed (bilateral primary and secondary somatosensory cortex) at various velocity contrasts (5 vs 25 cm/s, 5 vs 65 cm/s, and 25 vs 65 cm/s). The similarities and differences of FC among three velocities shed light on the neuronal networks encoding the orofacial tactile perception of velocity. [ABSTRACT FROM AUTHOR]

Antibacterial resistance is an issue of increasing severity as current antibiotics are losing their effectiveness and fewer antibiotics are being developed. New methods for combating bacterial virulence are required. Modulating molecular communication among bacteria can alter phenotype, including attachment to epithelia, biofilm formation, and even toxin production. Intercepting and modulating communication networks provide a means to attenuate virulence without directly interacting with the bacteria of interest. In this work, we target communication mediated by the quorum sensing (QS) bacterial autoinducer-2, AI-2. We have assembled a capsule of biological polymers alginate and chitosan, attached an AI-2 processing kinase, LsrK, and provided substrate, ATP, for enzymatic alteration of AI-2 in culture fluids. Correspondingly, AI-2 mediated QS activity is diminished. All components of this system are 'biofabricated'-they are biologically derived and their assembly is accomplished using biological means. Initially, component quantities and kinetics were tested as assembled in microtiter plates. Subsequently, the identical components and assembly means were used to create the 'artificial cell' capsules. The functionalized capsules, when introduced into populations of bacteria, alter the dynamics of the AI-2 bacterial communication, attenuating QS activated phenotypes. We envision the assembly of these and other capsules or similar materials, as means to alter QS activity in a biologically compatible manner and in many environments, including in humans. [ABSTRACT FROM AUTHOR]

Processing dynamic tactile inputs is a primary function of the somatosensory system. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of sensorimotor function following neurological insult. Little is known about tactile velocity encoding in mechanosensory trigeminal networks required for speech, suck, mastication, and facial gesture. High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile stimulation of perioral and buccal hairy skin in 20 neurotypical adults. A custom multichannel, scalable pneumotactile array consisting of 7 TAC-Cells was used to present 5 stimulus conditions: 5 cm/s, 25 cm/s, 65 cm/s, ALL-ON synchronous activation, and ALL-OFF. The spatiotemporal organization of whole-brain blood oxygen level-dependent (BOLD) response was analyzed with general linear modeling (GLM) and fitted response estimates of percent signal change to compare activations associated with each velocity, and the main effect of velocity alone. Sequential saltatory inputs to the right lower face produced localized BOLD responses in 6 key regions of interest (ROI) including; contralateral precentral and postcentral gyri, and ipsilateral precentral, superior temporal (STG), supramarginal gyri (SMG), and cerebellum. The spatiotemporal organization of the evoked BOLD response was highly dependent on velocity, with the greatest amplitude of BOLD signal change recorded during the 5 cm/s presentation in the contralateral hemisphere. Temporal analysis of BOLD response by velocity indicated rapid adaptation via a scalability of networks processing changing pneumotactile velocity cues. [ABSTRACT FROM AUTHOR]

Neurons in the somatosensory cortex are exquisitely sensitive to mechanical stimulation of the skin surface. The location, velocity, direction, and adaptation of tactile stimuli on the skin’s surface are discriminable features of somatosensory processing, however the representation and processing of dynamic tactile arrays in the human somatosensory cortex are poorly understood. The principal aim of this study was to map the relation between dynamic saltatory pneumatic stimuli at discrete traverse velocities on the glabrous hand and the resultant pattern of evoked BOLD response in the human brain. Moreover, we hypothesized that the hand representation in contralateral Brodmann Area (BA) 3b would show a significant dependence on stimulus velocity. Saltatory pneumatic pulses (60 ms duration, 9.5 ms rise/fall) were repetitively sequenced through a 7-channel TAC-Cell array at traverse velocities of 5, 25, and 65 cm/s on the glabrous hand initiated at the tips of D2 (index finger) and D3 (middle finger) and sequenced towards the D1 (thumb). The resulting hemodynamic response was sampled during 3 functional MRI scans (BOLD) in 20 neurotypical right-handed adults at 3T. Results from each subject were inserted to the one-way ANOVA within-subjects and one sample t-test to evaluate the group main effect of all three velocities stimuli and each of three different velocities, respectively. The stimulus evoked BOLD response revealed a dynamic representation of saltatory pneumotactile stimulus velocity in a network consisting of the contralateral primary hand somatosensory cortex (BA3b), associated primary motor cortex (BA4), posterior insula, and ipsilateral deep cerebellum. The spatial extent of this network was greatest at the 5 and 25 cm/s pneumotactile stimulus velocities. [ABSTRACT FROM AUTHOR]

When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve NC oral delivery to treat gastrointestinal (GI) pathologies or for systemic absorption. However, GI instability of targeting moieties compromises this strategy. This study explores whether encapsulation of antibody-coated NCs in microcapsules would protect against gastric degradation, providing NC release and targeting in intestinal conditions. Nanoparticles coated with antibodies against intercellular adhesion molecule-1 (anti-ICAM) or nonspecific immunoglobulin G (IgG) are encapsulated in chitosan (shell) - alginate (core) microcapsules. Encapsulation efficiency is >95% and NC relase from microcapsules in storage is <10%. There is minimal NC release at gastric pH (<10%) and burst release at intestinal pH (75%-85%). Encapsulated NCs afford increased protection against degradation (threefold to fourfold) and increased cell targeting (8-20-fold) after release versus the nonencapsulated NCs. Mouse oral gavage shows that microencapsulation provides 38%-65% greater protection of anti-ICAM NCs in the GI tract, 40% lower gastric retention, and fourfold to ninefold enhanced intestinal biodistribution versus nonencapsulated NCs. Therefore, microencapsulation of antibody-targeted NCs may enable active targeting strategies to be effective in the context of oral drug delivery. [ABSTRACT FROM AUTHOR]

Cortical adaptation to sustained sensory input is a pervasive form of short-term plasticity in neurological systems. Its role in sensory perception in health and disease, or predicting long-term plastic changes resulting from sensory training offers insight into the mechanisms of somatosensory and sensorimotor processing. A 4-channel electroencephalography (EEG) recording montage was placed bilaterally (C3-P3, C4-P4, F7-P3, F8-P4) to characterize the short-term effects of pulsed pneumatic orofacial stimulation on the cortical somatosensory evoked potential (cSEP) in twenty neurotypical adults (mean age=21±2.88 years). A servo-controlled pneumatic amplifier was used to deliver a repetitive series of pneumatic pulse trains (six 50-ms pulses, 5-second intertrain interval) through a linked pair of custom acetal homopolymer probes ( aka TAC-Cells) adhered to the nonglabrous skin of the lower face proximal to the right oral angle to synchronously activate mechanoreceptive afferents in the trigeminal nerve. Blocks of pulse trains were counterbalanced among participants and delivered at two rates, 2 and 4 Hz. TAC-Cell stimulation of the lower face consistently evoked a series of cSEPs at P7, N20, P28, N38, P75, N85, and P115. The spatial organization and adaptation of the evoked cSEP was dependent on stimulus pulse index (1–6 within the pulse train, p =.012), frequency of stimulus presentation (2 vs 4 Hz, p <.001), component (P7-P115, p <.001), and recording montage (channels 1–4, p <.001). Early component latencies (P7-N20) were highly stable in polarity (sign) and latency, and consistent with putative far-field generators (e.g., trigeminal brainstem, ventroposteromedial thalamus). [ABSTRACT FROM AUTHOR]

A polypyrrole nanotube containing nanoparticles is prepared by a dual template approach, and the inside of the nanotube is selectively functionalized with carboxyl and amine groups. [ABSTRACT FROM AUTHOR]

• Introducing a TMS coil into the scanner environment can result in image artifacts. • PSF-EPI is a general strategy for handling susceptibility artifacts and distortion. • TMS-related artifacts are reduced in PSF-corrected compared to uncorrected data. • PSF-EPI can be used for concurrent TMS-fMRI and resting-state fMRI scans. Transcranial magnetic stimulation (TMS) can be paired with functional magnetic resonance imaging (fMRI) in concurrent TMS-fMRI experiments. These multimodal experiments enable causal probing of network architecture in the human brain which can complement alternative network mapping approaches. Critically, merely introducing the TMS coil into the scanner environment can sometimes produce substantial magnetic field inhomogeneities and spatial distortions which limit the utility of concurrent TMS-fMRI. We assessed the efficacy of point spread function corrected echo planar imaging (PSF-EPI) in correcting for the field inhomogeneities associated with a TMS coil at 3 T. In phantom and brain scans, we quantitatively compared the coil-induced distortion artifacts measured in EPI scans with and without PSF correction. We found that the application of PSF corrections to the EPI data significantly improved signal-to-noise and reduced distortions. In phantom scans with the PSF-EPI sequence, we also characterized the temporal profile of dynamic artifacts associated with TMS delivery and found that image quality remained high as long as the TMS pulse preceded the RF excitation pulses by at least 50 ms. Lastly, we validated the PSF-EPI sequence in human brain scans involving TMS and motor behavior as well as resting state fMRI scans. Our collective results demonstrate the potential benefits of PSF-EPI for concurrent TMS-fMRI when coil-related artifacts are a concern. The ability to collect high quality resting state fMRI data in the same session as the concurrent TMS-fMRI experiment offers a unique opportunity to interrogate network architecture in the human brain. [ABSTRACT FROM AUTHOR]

On page 3382, S. Muro and co‐workers explore the protective effects of a chitosan shell against gastric degradation of orally administered drug nanocarriers. Antibodies targeted to the intestine are loaded into alginate nanocarriers and encapsulated with chitosan. The encapsulation improves delivery to the target, by protecting against the effects of gastric conditions, promoting higher targeting to the intestinal region. [ABSTRACT FROM AUTHOR]

We have developed microscale polymer capsules that are able to chemically degrade a certain type of polymeric microbead in their immediate vicinity. The inspiration here is from the body's immune system, where killer T cells selectively destroy cancerous cells or cells infected by pathogens while leaving healthy cells alone. The "killer" capsules are made from the cationic biopolymer chitosan by a combination of ionic cross-linking (using multivalent tripolyposphate anions) and subsequent covalent cross-linking (using glutaraldehyde). During capsule formation, the enzyme glucose oxidase (GOx) is encapsulated in these capsules. The target beads are made by ionic cross-linking of the biopolymer alginate using copper (Cu 2+ ) cations. The killer capsules harvest glucose from their surroundings, which is then enzymatically converted by GOx into gluconate ions. These ions are known for their ability to chelate Cu 2+ cations. Thus, when a killer capsule is next to a target alginate bead, the gluconate ions diffuse into the bead and extract the Cu 2+ cross-links, causing the disintegration of the target bead. Such destruction is visualized in real-time using optical microscopy. The destruction is specific, i.e., other microparticles that do not contain Cu 2+ are left undisturbed. Moreover, the destruction is localized, i.e., the targets destroyed in the short term are the ones right next to the killer beads. The time scale for destruction depends on the concentration of encapsulated enzyme in the capsules.

Recently there has been much interest in using light to activate self-assembly of molecules in a fluid, leading to gelation. The advantage of light over other stimuli lies in its spatial selectivity, i.e., its ability to be directed at a precise location, which could be particularly useful in microfluidic applications. However, existing light-responsive fluids are not suitable for these purposes since they do not convert into sufficiently strong gels that can withstand shear. Here, we address this deficiency by developing a new light-responsive system based on the well-known polysaccharide, alginate. The fluid is composed entirely of commercially available components: alginate, a photoacid generator (PAG), and a chelated complex of divalent strontium (Sr(2+)) cations. Upon exposure to ultraviolet (UV) light, the PAG dissociates to release H(+) ions, which in turn induce the release of free Sr(2+) from the chelate. The Sr(2+) ions self-assemble with the alginate chains to give a stiff gel with an elastic modulus ∼2000 Pa and a yield stress ∼400 Pa (this gel is strong enough to be picked up and held by one's fingers). The above fluid is sent through a network of microchannels and a short segment of a specific channel is exposed to UV light. At that point, the fluid is locally transformed into a strong gel in a few minutes, and the resulting gel blocks the flow through that channel while other channels remain open. When the UV light is removed, the gel is gradually diluted by the flow and the channel reopens. We have thus demonstrated a remote-controlled fluidic valve that can be closed by shining light and reopened when the light is removed. In addition, we also show that light-induced gelation of our alginate fluid can be used to deposit biocompatible payloads at specific addresses within a microchannel.

We describe the creation of polymeric microcapsules that can exhibit autonomous motion along defined trajectories. The capsules are made by cross-linking aqueous microdroplets of the biopolymer chitosan using glutaraldehyde. A coflow microfluidic tubing device is used to generate chitosan droplets containing nanoparticles (NPs) with an iron (Fe) core and a platinum (Pt) shell. The droplets are then incubated in a Petri dish with the cross-linking solution, and an external magnet is placed below the Petri dish to pull the NPs together as a collective "patch" on one end of each droplet. This results in cross-linked capsules (∼150 μm in diameter) with an anisotropic (patchy) structure. When these capsules are placed in a solution of H2O2, the Pt shell of the NPs catalyzes the decomposition of H2O2 into O2 gas, which is ejected from the patchy end in the form of bubbles. As a result, the capsules (which are termed micromotors) move in a direction opposite to the bubbles. Furthermore, the micromotors can be steered along specific paths by an external magnet (the magnetic response arises due to the Fe in the core of the NPs). A given micromotor can thus be directed to meet with and adhere to an inert capsule, i.e., a model cargo. Adhesion occurs due to the soft nature of the two structures. Once the cargo is picked up, the micromotor-cargo pair can be moved along a specific path to a destination, whereupon the cargo can be released from the micromotor. We believe these soft micromotors offer significant benefits over their existing hard counterparts because of their biocompatibility, biodegradability, and ability to encapsulate a variety of payloads.

Molecular organogelators convert oils into gels by forming self-assembled fibrous networks. Here, we demonstrate that such gelation can be activated by contacting the oil with an immiscible solvent (water). Our gelator is dibenzylidene sorbitol (DBS), which forms a low-viscosity sol when added to toluene containing a small amount of dimethyl sulfoxide (DMSO). Upon contact with water, DMSO partitions into the water, activating gelation of DBS in the toluene. The gel grows from the oil/water interface and slowly envelops the oil phase. We have exploited this effect for the self-repair of oil leaks from underwater tubes. When a DBS/toluene/DMSO solution flows through the tube, it forms a gel selectively at the leak point, thereby plugging the leak and restoring flow. Our approach is reminiscent of wound-sealing via blood-clotting: there also, inactive gelators in blood are activated at the wound site into a fibrous network, thereby plugging the wound and restoring blood flow.

The ability to modulate the physical properties of a supramolecular hydrogel may be beneficial for biomaterial and biomedical applications. We find that guanosine (G 1), when combined with 0.5 equiv of potassium borate, forms a strong, self-supporting hydrogel with elastic moduli >10 kPa. The countercation in the borate salt (MB(OH)4) significantly alters the physical properties of the hydrogel. The gelator combination of G 1 and KB(OH)4 formed the strongest hydrogel, while the weakest system was obtained with LiB(OH)4, as judged by (1)H NMR and rheology. Data from powder XRD, (1)H double-quantum solid-state magic-angle spinning (MAS) NMR and small-angle neutron scattering (SANS) were consistent with a structural model that involves formation of borate dimers and G4·K(+) quartets by G 1 and KB(OH)4. Stacking of these G4·M(+) quartets into G4-nanowires gives a hydrogel. We found that the M(+) cation helps stabilize the anionic guanosine-borate (GB) diesters, as well as the G4-quartets. Supplementing the standard gelator mixture of G 1 and 0.5 equiv of KB(OH)4 with additional KCl or KNO3 increased the strength of the hydrogel. We found that thioflavin T fluoresces in the presence of G4·M(+) precursor structures. This fluorescence response for thioflavin T was the greatest for the K(+) GB system, presumably due to the enhanced interaction of the dye with the more stable G4·K(+) quartets. The fluorescence of thioflavin T increased as a function of gelator concentration with an increase that correlated with the system's gel point, as measured by solution viscosity.

The self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Previous studies on lecithin-bile salt mixtures have reported the formation of short, rodlike micelles. Here, we show that lecithin-bile salt micelles can be further induced to grow into long, flexible wormlike structures. The formation of long worms and their resultant entanglement into transient networks is reflected in the rheology: the fluids become viscoelastic and exhibit Maxwellian behavior, and their zero-shear viscosity can be up to a 1000-fold higher than that of water. The presence of worms is further confirmed by data from small-angle neutron and X-ray scattering and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin, which suggests a strong binding interaction between the two species. In addition, micellar growth also requires a sufficient concentration of background electrolyte such as NaCl or sodium citrate that serves to screen the electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We postulate a mechanism based on changes in the molecular geometry caused by bile salts and electrolytes to explain the micellar growth.

The precocial nature of orofacial sensorimotor control underscores the biological importance of establishing ororythmic activity in human infants. The purpose of this study was to assess the effects of comparable doses of three forms of orosensory experience, including a low-velocity spectrally reduced orocutaneous stimulus (NT1), a high-velocity broad spectrum orocutaneous stimulus (NT2), and a SHAM stimulus consisting of a blind pacifier. Each orosensory experience condition was paired with gavage feedings 3x/day for 10 days in the neonatal intensive care unit (NICU). Four groups of preterm infants (N=214), including those with respiratory distress syndrome (RDS), chronic lung disease (CLD), infants of diabetic mothers (IDM), and healthy controls (HI) were randomized to the type of orosensory condition. Mixed modeling, adjusted for gender, gestational age, postmenstrual age, and birth weight, demonstrated the most significant gains in non-nutritive suck (NNS) development among CLD infants who were treated with the NT2 stimulus, with smaller gains realized among RDS and IDM infants. The broader spectrum of the NT2 stimulus maps closely to known response properties of mechanoreceptors in lip, tongue, and oral mucosa and is more effective in promoting NNS development among preterm infants with impaired oromotor function compared to the low-velocity, spectrally reduced NT1 orosensory stimulus.

A photoresponsive micellar solution is developed as a promising working fluid for district heating/cooling systems (DHCs). It can be reversibly switched between a drag reduction (DR) mode and an efficient heat transfer (EHT) mode by light irradiation. The DR mode is advantageous during fluid transport, and the EHT mode is favored when the fluid passes through heat exchangers. This smart fluid is an aqueous solution of cationic surfactant oleyl bis(2-hydroxyethyl)methyl ammonium chloride (OHAC, 3.4 mM) and the sodium salt of 4-phenylazo benzoic acid (ACA, 2 mM). Initially, ACA is in a trans configuration and the OHAC/ACA solution is viscoelastic and exhibits DR (of up to 80% relative to pure water). At the same time, this solution is not effective for heat transfer. Upon UV irradiation, trans-ACA is converted to cis-ACA, and in turn, the solution is converted to its EHT mode (i.e., it loses its viscoelasticity and DR) but it now has a heat-transfer capability comparable to that of water. Subsequent irradiation with visible light reverts the fluid to its viscoelastic DR mode. The above property changes are connected to photoinduced changes in the nanostructure of the fluid. In the DR mode, the OHAC/trans-ACA molecules assemble into long threadlike micelles that impart viscoelasticity and DR capability to the fluid. Conversely, in the EHT mode the mixture of OHAC and cis-ACA forms much shorter cylindrical micelles that contribute to negligible viscoelasticity and effective heat transfer. These nanostructural changes are confirmed by cryo-transmission electron microscopy (cryo-TEM), and the photoisomerization of trans-ACA and cis-ACA is verified by (1)H NMR.

Biopolymers bearing hydrophobic side-chains, such as hydrophobically modified chitosan (hmC), can connect liposomes into a gel network via hydrophobic interactions. In this paper, we show that such liposome gels possess an attractive combination of properties for certain drug delivery applications. Their shear-thinning property allows these gels to be injected at a particular site, while their gel-like nature at rest ensures that the material will remain localized at that site. Moreover, drugs can be encapsulated in the interior of the liposomes and delivered at the local site for an extended period of time. The presence of two transport resistances - from the liposomal bilayer and the gel network - is shown to be responsible for the sustained release; in turn, disruption of the liposomes both weakens the gel and causes a faster release. We have monitored release kinetics from liposome gels of a cationic anticancer drug doxorubicin (Dox) encapsulated in liposomes. Sustained release of Dox from these gels and the concomitant cytotoxic effect could be observed for over a week.

Helical tubules are a fascinating and an intriguing class of self-assemblies. They occur frequently in biology and are believed to be intermediates in formation of gallstones. The pathway by which amphiphiles transform from an initial state of vesicles or micelles into such tubules has puzzled soft matter physicists, and it has raised important questions about the interplay between molecular chirality and self-assembly. Here, for the first time, we demonstrate direct, real-time observations by light microscopy of the pathway to helical microtubules from an initial solution of nanoscale vesicles. The tubules are formed in aqueous mixtures of the single-tailed diacetylenic surfactant, 10,12-pentacosadiynoic acid (PCDA), and a short-chain alcohol. The stepwise process involves nucleation of thin helical microribbons from the vesicle solution. These ribbons then thicken, rearrange, and fold into closed tubules. Subsequently, most tubules further rearrange into plate-like structures, and once again, we are able to visualize this process in real time. A notable aspect of the above system is that the precursors are achiral; yet, the tubules are formed from helical ribbons. Our study provides new insights into tubule formation that will be valuable in clarifying and refining theoretical models for these fascinating structures.