Programmable interactions with biomimetic DNA linkers at fluid membranes and interfaces

At the heart of the structured architecture and complex dynamics of biological systems are specific and timely interactions operated by biomolecules. In many instances, biomolecular agents are spatially confined to flexible lipid membranes where, among other functions, they control cell adhesion, motility and tissue formation. Besides being central to several biological processes, \emph{multivalent interactions} mediated by reactive linkers confined to deformable substrates underpin the design of synthetic-biological platforms and advanced biomimetic materials. Here we review recent advances on the experimental study and theoretical modelling of a heterogeneous class of biomimetic systems in which synthetic linkers mediate multivalent interactions between fluid and deformable colloidal units, including lipid vesicles and emulsion droplets. Linkers are often prepared from synthetic DNA nanostructures, enabling full programmability of the thermodynamic and kinetic properties of their mutual interactions. The coupling of the statistical effects of multivalent interactions with substrate fluidity and deformability gives rise to a rich emerging phenomenology that, in the context of self-assembled soft materials, has been shown to produce exotic phase behaviour, stimuli-responsiveness, and kinetic programmability of the self-assembly process. Applications to (synthetic) biology will also be reviewed.Comment: 63 pages, revie

Reaction-Diffusion Patterning of DNA-Based Artificial Cells

Biological cells display complex internal architectures with distinct micro environments that establish the chemical heterogeneity needed to sustain cellular functions. The continued efforts to create advanced cell mimics, namely, artificial cells, demands strategies for constructing similarly heterogeneous structures with localized functionalities. Here, we introduce a platform for constructing membraneless artificial cells from the self-assembly of synthetic DNA nanostructures in which internal domains can be established thanks to prescribed reaction-diffusion waves. The method, rationalized through numerical modeling, enables the formation of up to five distinct concentric environments in which functional moieties can be localized. As a proof-of-concept, we apply this platform to build DNA-based artificial cells in which a prototypical nucleus synthesizes fluorescent RNA aptamers that then accumulate in a surrounding storage shell, thus demonstrating the spatial segregation of functionalities reminiscent of that observed in biological cells

Membrane Scaffolds Enhance the Responsiveness and Stability of DNA-Based Sensing Circuits.

Target-induced DNA strand displacement is an excellent candidate for developing analyte-responsive DNA circuitry to be used in clinical diagnostics and synthetic biology. While most available technologies rely on DNA circuitry free to diffuse in bulk, here we explore the use of liposomes as scaffolds for DNA-based sensing nanodevices. Our proof-of-concept sensing circuit responds to the presence of a model target analyte by releasing a DNA strand, which in turn activates a fluorescent reporter. Through a combination of experiments and coarse-grained Monte Carlo simulations, we demonstrate that the presence of the membrane scaffold accelerates the process of oligonucleotide release and suppresses undesired leakage reactions, making the sensor both more responsive and robust

Amphiphilic DNA nanostructures for bottom-up synthetic biology

DNA nanotechnology enables the construction of sophisticated biomimetic nanomachines that are increasingly central to the growing efforts of creating complex cell-like entities from the bottom-up. DNA nanostructures have been proposed as both structural and functional elements of these artificial cells, and in many instances are decorated with hydrophobic moieties to enable interfacing with synthetic lipid bilayers or regulating bulk self-organisation. In this feature article we review recent efforts to design biomimetic membrane-anchored DNA nanostructures capable of imparting complex functionalities to cell-like objects, such as regulated adhesion, tissue formation, communication and transport. We then discuss the ability of hydrophobic modifications to enable the self-assembly of DNA-based nanostructured frameworks with prescribed morphology and functionality, and explore the relevance of these novel materials for artificial cell science and beyond. Finally, we comment on the yet mostly unexpressed potential of amphiphilic DNA-nanotechnology as a complete toolbox for bottom-up synthetic biology – a figurative and literal scaffold upon which the next generation of synthetic cells could be built

Three Essays in Insider Trading.

This dissertation investigates insider trading around significant corporate information events. Chapter 1 tests the prediction of standard option pricing models that there is no relation between past stock returns and stock option prices. Using individual stock options data, we show that puts are significantly overvalued relative to calls after large stock price increases and calls are significantly overvalued after large stock price decreases. This is exactly opposite to what we have observed in index options. We argue that it is the autocorrelation structure of the individual stock returns that drives this valuation effect, which areboth economically and statistically significant. Overall, our results suggest that past stock returns exert an important influence on individual stock option prices. Chapter 2 investigates trading volume and profitability of insider trades around scheduled versus unscheduled corporate announcements to explore how corporate insiders utilize their private information when there is dispersion in the amount of liquidity trading. I show that corporate insiders trade more heavily before unscheduled corporate announcements as compared to scheduled announcements. Also insider trades before unscheduled announcements are much more profitable than those before scheduled announcements. This evidence clearly suggests that corporate insiders time their trades around material corporate information events based on the amount of liquidity trading available to camouflage their trades. I also relate this finding to private information and test whether PIN captures information asymmetry around such events. I find that PIN is much higher before unscheduled announcements than before scheduled ones. Chapter 3 examines option trading before significant information events. Using a broad sample of merger announcements, I find that there is abnormal option trading prior to such announcements after controlling for merger characteristics. This abnormal option trading is mainly concentrated in short-term and at-the-money options. Trading volume in these options leads stock market order imbalances and strongly contributes to the pre-takeover stock price runup. Implied volatility spread calculated from these options is strongly positively associated with the abnormal option volume. Finally, I also investigate whether option volume can be used to predict takeover targets. I find strong predictive power of option volume for takeover targets.Ph.D.Business AdministrationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60730/1/xuewuw_1.pd

Artificial Compartments Encapsulating Enzymatic Reactions: Towards the Construction of Artificial Organelles

Cells have used compartmentalization to implement complex biological processes involving thousands of enzyme cascade reactions. Enzymes are spatially organized into the cellular compartments to carry out specific and efficient reactions in a spatiotemporally controlled manner. These compartments are divided into membrane-bound and membraneless organelles. Mimicking such cellular compartment systems has been a challenge for years. A variety of artificial scaffolds, including liposomes, polymersomes, proteins, nucleic acids, or hybrid materials have been used to construct artificial membrane-bound or membraneless compartments. These artificial compartments may have great potential for applications in biosynthesis, drug delivery, diagnosis and therapeutics, among others. This review first summarizes the typical examples of cellular compartments. In particular, the recent studies on cellular membraneless organelles (biomolecular condensates) are reviewed. We then summarize the recent advances in the construction of artificial compartments using engineered platforms. Finally, we provide our insights into the construction of biomimetic systems and the applications of these systems. This review article provides a timely summary of the relevant perspectives for the future development of artificial compartments, the building blocks for the construction of artificial organelles or cells

Hierarchical dynamics of individual RNA helix base pair formation and disruption

This thesis explores the RNA folding problem using single-molecule field effect transistors (smFETs) to measure the lifetimes of individual RNA base-pairing rearrangements. In the course of this research, considerable computational, chemical, and engineering contributions were developed so that the single-molecule measurements could be conducted and quantified. These advancements have allowed, on the basis of the smFET data collected herein, the quantification of a kinetic model for RNA stem-loop structures which has been generalized to quantitatively explore the phenomenological observation that an RNA found in the bacillus subtilis strain acts as a metabolite-sensing switch, allowing RNA polymerase to transcribe the messenger RNA when the metabolite is present and preventing transcription when the metabolite is absent. Together, the data presented quantify a simple model for the base pairing rearrangements that underlie RNA folding

Institutional cross-ownership and corporate strategy: the case of mergers and acquisitions

This article provides new evidence on the important role of institutional investors in affecting corporate strategy. Institutional cross-ownership between two firms not only increases the probability of them merging, but also affects the outcomes of mergers and acquisitions (M&As). Institutional cross-ownership reduces deal premiums, increases stock payment in M&A transactions, and lowers the completion probabilities of deals with negative acquirer announcement returns. Furthermore, deals with high institutional cross-ownership have lower transaction costs and disclose more transparent financial statement information. The effect of cross-ownership on the total deal synergies and post-deal long-term performance is positive, which can be attributed to independent and non-transient cross-owners. Our findings are robust after mitigating the cross-ownership asymmetry concern. Overall, our results suggest that the growth of institutional cross-holdings in U.S. stock markets may greatly change corporate strategies and decision-making processes