Microtube self-assembly leads to conformational freezing point depression.

HYPOTHESIS: Multi-walled tubular aggregates formed by hierarchical self-assembly of beta-cyclodextrin (ß-CD) and sodium dodecylsulfate (SDS) hold a great potential as microcarriers. However, the underlying mechanism for this self-assembly is not well understood. To advance the application of these structures, it is essential to fine-tune the cavity size and comprehensively elucidate the energetic balance driving their formation: the bending modulus versus the microscopic line tension. EXPERIMENTS: We investigated temperature-induced changes in the hierarchical tubular aggregates using synchrotron small-angle X-ray scattering across a broad concentration range. Detailed analysis of the scattering patterns enabled us to determine the structural parameters of the microtubes and to construct a phase diagram of the system. FINDINGS: The microtubes grow from the outside in and melt from the inside out. We relate derived structural parameters to enthalpic changes driving the self-assembly process on the molecular level in terms of their bending modulus and microscopic line tension. We find that the conformation of the crystalline bilayer affects the saturation concentration, providing an example of a phenomenon we call conformational freezing point depression. Inspired by the colligative phenomenon of freezing point depression, well known from undergraduate physics, we model this system by including the membrane conformation, which can describe the energetics of this hierarchical system and give access to microscopic properties without free parameters.

Transcription factor competition facilitates self-sustained oscillations in single gene genetic circuits.

Genetic feedback loops can be used by cells to regulate internal processes or to keep track of time. It is often thought that, for a genetic circuit to display self-sustained oscillations, a degree of cooperativity is needed in the binding and unbinding of actor species. This cooperativity is usually modeled using a Hill function, regardless of the actual promoter architecture. Furthermore, genetic circuits do not operate in isolation and often transcription factors are shared between different promoters. In this work we show how mathematical modelling of genetic feedback loops can be facilitated with a mechanistic fold-change function that takes into account the titration effect caused by competing binding sites for transcription factors. The model shows how the titration effect facilitates self-sustained oscillations in a minimal genetic feedback loop: a gene that produces its own repressor directly without cooperative transcription factor binding. The use of delay-differential equations leads to a stability contour that predicts whether a genetic feedback loop will show self-sustained oscillations, even when taking the bursty nature of transcription into account.

Repulsive and attractive depletion forces mediated by nonadsorbing polyelectrolytes in the Donnan limit.

In mixtures of colloids and nonadsorbing polyelectrolytes, a Donnan potential arises across the region between surfaces that are depleted of the polyelectrolyte and the rest of the system. This Donnan potential tends to shift the polyelectrolyte density profile toward the colloidal surface and leads to the local accumulation of polyelectrolytes. We derive a zero-field theory for the disjoining pressure between two parallel flat plates. The polyelectrolyte is allowed to enter the confined interplate region at the cost of a conformational free energy penalty. The resulting disjoining pressure shows a crossover to a repulsive regime when the interplate separation gets smaller than the size of the polyelectrolyte chain, followed by an attractive part. We find a quantitative match between the model and self-consistent field computations that take into account the full Poisson-Boltzmann electrostatics.

Inward growth by nucleation: Multiscale self-assembly of ordered membranes.

Striking morphological similarities found between superstructures of a wide variety of seemingly unrelated crystalline membrane systems hint at the existence of a common formation mechanism. Resembling systems such as multiwalled carbon nanotubes, bacterial protein shells, or peptide nanotubes, the self-assembly of SDS/ß-cyclodextrin complexes leads to monodisperse multilamellar microtubes. We uncover the mechanism of this hierarchical self-assembly process by time-resolved small- and ultrasmall-angle x-ray scattering. In particular, we show that symmetric crystalline bilayers bend into hollow cylinders as a consequence of membrane line tension and an anisotropic elastic modulus. Starting from single-walled microtubes, successive nucleation of new cylinders inside preexisting ones drives an inward growth. As both the driving forces that underlie the self-assembly behavior and the resulting morphologies are common to systems of ordered membranes, we believe that this formation mechanism has a similarly general applicability.

Self-consistent theory of transcriptional control in complex regulatory architectures.

Individual regulatory proteins are typically charged with the simultaneous regulation of a battery of different genes. As a result, when one of these proteins is limiting, competitive effects have a significant impact on the transcriptional response of the regulated genes. Here we present a general framework for the analysis of any generic regulatory architecture that accounts for the competitive effects of the regulatory environment by isolating these effects into an effective concentration parameter. These predictions are formulated using the grand-canonical ensemble of statistical mechanics and the fold-change in gene expression is predicted as a function of the number of transcription factors, the strength of interactions between the transcription factors and their DNA binding sites, and the effective concentration of the transcription factor. The effective concentration is set by the transcription factor interactions with competing binding sites within the cell and is determined self-consistently. Using this approach, we analyze regulatory architectures in the grand-canonical ensemble ranging from simple repression and simple activation to scenarios that include repression mediated by DNA looping of distal regulatory sites. It is demonstrated that all the canonical expressions previously derived in the case of an isolated, non-competing gene, can be generalised by a simple substitution to their grand canonical counterpart, which allows for simple intuitive incorporation of the influence of multiple competing transcription factor binding sites. As an example of the strength of this approach, we build on these results to present an analytical description of transcriptional regulation of the lac operon.

In situ observation of self-assembly of sugars and surfactants from nanometres to microns.

The hierarchical self-assembly of sugar and surfactant molecules into hollow tubular microstructures was characterized in situ with high resolution small-angle X-ray scattering spanning more than three orders of magnitude of spatial scales. Scattering profiles reveal that aqueous host-guest inclusion complexes self-assemble into multiple equally spaced curved bilayers forming a collection of concentric hollow cylinders. Scattering data can be described by a simple theoretical model of the microtubes. The interlamellar distance was found to be surprisingly large. Moreover, we report that the multi-walled structure of the microtubes swells as the concentration or the temperature is varied.

Effects of added silica nanoparticles on the nematic liquid crystal phase formation in beidellite suspensions.

In this article, we present a study of the liquid crystal phase behavior of mixed suspensions of the natural smectite clay mineral beidellite and nonadsorbing colloidal silica particles. While virtually all smectite clays dispersed in water form gels at very low concentrations, beidellite displays a first order isotropic-nematic phase transition before gel formation (J. Phys. Chem. B, 2009, 113, 15858-15869). The addition of silica nanospheres shifts the concentrations of the coexisting isotropic and nematic phases to slightly higher values while at the same time markedly accelerating the phase separation process. Furthermore, beidellite suspensions at volume fractions above the isotropic-nematic phase separation, trapped in a kinetically arrested gel state, liquefy on the addition of silica nanospheres and proceed to isotropic-nematic phase separation. Using small-angle X-ray scattering (SAXS), we probe the structural changes caused by the addition of the silica nanospheres, and we relate the modification of the phase transition kinetics to the change of the rheological properties.