抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

In this review, we survey the diversity of structures and functions which are encountered in advanced self-assembled nanomaterials. We highlight their flourishing implementations in three active domains of applications: biomedical sciences, information technologies, and environmental sciences. Our main objective is to provide the reader with a concise and straightforward entry to this broad field by selecting the most recent and important research articles, supported by some more comprehensive reviews to introduce each topic. Overall, this compilation illustrates how, based on the rules of supramolecular chemistry, the bottom-up approach to design functional objects at the nanoscale is currently producing highly sophisticated materials oriented towards a growing number of applications with high societal impact.

https://pubs.rsc.org/en/content/articlepdf/2013/NR/C3NR02176A

Supramolecular self-assemblies as functional nanomaterials

From Cascaded Catalytic Nucleic Acids to Enzyme–DNA Nanostructures: Controlling Reactivity, Sensing, Logic Operations, and Assembly of Complex Structures

Developing powerful, simple and low-cost DNA amplification techniques is of great significance to bioanalysis and biomedical research Thus far, many signal amplification strategies have been developed, such as polymerase chain reaction (PCR), rolling circle amplification (RCA), and DNA strand displacement amplification (SDA) In particular, hybridization chain reaction (HCR), a type of toehold-mediated strand displacement (TMSD) reaction, has attracted great interest because of its enzyme-free nature, isothermal conditions, simple protocols, and excellent amplification efficiency In a typical HCR, an analyte initiates the cross-opening of two DNA hairpins, yielding nicked double helices that are analogous to alternating copolymers As an efficient amplification platform, HCR has been utilized for the sensitive detection of a wide variety of analytes, including nucleic acids, proteins, small molecules, and cells In recent years, more complicated sets of monomers have been designed to develop nonlinear HCR, such as branched HCR and even dendritic systems, achieving quadratic and exponential growth mechanisms In addition, HCR has attracted enormous attention in the fields of bioimaging and biomedicine, including applications in fluorescence in situ hybridization (FISH) imaging, live cell imaging, and targeted drug delivery In this review, we introduce the fundamentals of HCR and examine the visualization and analysis techniques for HCR products in detail The most recent HCR developments in biosensing, bioimaging, and biomedicine are subsequently discussed with selected examples Finally, the review provides insight into the challenges and future perspectives of HCR

Hybridization chain reaction: a versatile molecular tool for biosensing, bioimaging, and biomedicine

Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of strand displacement kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding has remained elusive. Here, we study strand displacement at multiple levels of detail, using an intuitive model of a random walk on a 1D energy landscape, a secondary structure kinetics model with single base-pair steps and a coarse-grained molecular model that incorporates 3D geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Two factors explain the dependence of strand displacement kinetics on toehold length: (i) the physical process by which a single step of branch migration occurs is significantly slower than the fraying of a single base pair and (ii) initiating branch migration incurs a thermodynamic penalty, not captured by state-of-the-art nearest neighbor models of DNA, due to the additional overhang it engenders at the junction. Our findings are consistent with previously measured or inferred rates for hybridization, fraying and branch migration, and they provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.

/pdf/on-the-biophysics-and-kinetics-of-toehold-mediated-dna-2y6hr2z023.pdf

On the biophysics and kinetics of toehold-mediated DNA strand displacement

Hybridization of DNA strands can be used to build molecular devices, and control of the kinetics of DNA hybridization is a crucial element in the design and construction of functional and autonomous devices. Toehold-mediated strand displacement has proved to be a powerful mechanism that allows programmable control of DNA hybridization. So far, attempts to control hybridization kinetics have mainly focused on the length and binding strength of toehold sequences. Here we show that insertion of a spacer between the toehold and displacement domains provides additional control: modulation of the nature and length of the spacer can be used to control strand-displacement rates over at least 3 orders of magnitude. We apply this mechanism to operate displacement reactions in potentially useful kinetic regimes: the kinetic proofreading and concentration-robust regimes.

http://nablab.rice.edu/publications/JACS2011_remote.pdf

Remote Toehold: A Mechanism for Flexible Control of DNA Hybridization Kinetics

We report reversible logic circuits made of DNA. The circuits are based on an AND gate that is designed to be thermodynamically and kinetically reversible and to respond nonlinearly to the concentrations of its input molecules. The circuits continuously recompute their outputs, allowing them to respond to changing inputs. They are robust to imperfections in their inputs.

/pdf/reversible-logic-circuits-made-of-dna-3qscvjw2rx.pdf

Reversible Logic Circuits Made of DNA

Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

High-resolution mapping of bifurcations in nonlinear biochemical circuits

Combinatorial displacement of DNA strands: application to matrix multiplication and weighted sums.

Cells rely on limited resources such as enzymes or transcription factors to process signals and make decisions. However, independent cellular pathways often compete for a common molecular resource. Competition is difficult to analyze because of its nonlinear global nature, and its role remains unclear. Here we show how decision pathways such as transcription networks may exploit competition to process information. Competition for one resource leads to the recognition of convex sets of patterns, whereas competition for several resources (overlapping or cascaded regulons) allows even more general pattern recognition. Competition also generates surprising couplings, such as correlating species that share no resource but a common competitor. The mechanism we propose relies on three primitives that are ubiquitous in cells: multiinput motifs, competition for a resource, and positive feedback loops.

Anthony J. Genot

Papers

Remote Toehold: A Mechanism for Flexible Control of DNA Hybridization Kinetics

Reversible Logic Circuits Made of DNA

High-resolution mapping of bifurcations in nonlinear biochemical circuits

Combinatorial displacement of DNA strands: application to matrix multiplication and weighted sums.

Computing with competition in biochemical networks.