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

The widespread use of molecular machines in biology has long suggested that great rewards could come from bridging the gap between synthetic molecular systems and the machines of the macroscopic world. In the last two decades, it has proved possible to design synthetic molecular systems with architectures where triggered large amplitude positional changes of submolecular components occur. Perhaps the best way to appreciate the technological potential of controlled molecular-level motion is to recognize that nanomotors and molecular-level machines lie at the heart of every significant biological process. Over billions of years of evolution, nature has not repeatedly chosen this solution for performing complex tasks without good reason. When mankind learns how to build artificial structures that can control and exploit molecular level motion and interface their effects directly with other molecular-level substructures and the outside world, it will potentially impact on every aspect of functional molecule and materials design. An improved understanding of physics and biology will surely follow.

The first steps on the long path to the invention of artificial molecular machines were arguably taken in 1827 when the Scottish botanist Robert Brown observed the haphazard motion of tiny particles under his microscope.1,2 The explanation for Brownian motion, that it is caused by bombardment of the particles by molecules as a consequence of the kinetic theory of matter, was later provided by Einstein, followed by experimental verification by Perrin.3,4 The random thermal motion of molecules and its implications for the laws of thermodynamics in turn inspired Gedankenexperiments (“thought experiments”) that explored the interplay (and apparent paradoxes) of Brownian motion and the Second Law of Thermodynamics. Richard Feynman’s famous 1959 lecture “There’s plenty of room at the bottom” outlined some of the promise that manmade molecular machines might hold.5,6 However, Feynman’s talk came at a time before chemists had the necessary synthetic and analytical tools to make molecular machines. While interest among synthetic chemists began to grow in the 1970s and 1980s, progress accelerated in the 1990s, particularly with the invention of methods to make mechanically interlocked molecular systems (catenanes and rotaxanes) and control and switch the relative positions of their components.7−24

Here, we review triggered large-amplitude motions in molecular structures and the changes in properties these can produce. We concentrate on conformational and configurational changes in wholly covalently bonded molecules and on catenanes and rotaxanes in which switching is brought about by various stimuli (light, electrochemistry, pH, heat, solvent polarity, cation or anion binding, allosteric effects, temperature, reversible covalent bond formation, etc.). Finally, we discuss the latest generations of sophisticated synthetic molecular machine systems in which the controlled motion of subcomponents is used to perform complex tasks, paving the way to applications and the realization of a new era of “molecular nanotechnology”.

1.1. The Language Used To Describe Molecular Machines
Terminology needs to be properly and appropriately defined and these meanings used consistently to effectively convey scientific concepts. Nowhere is the need for accurate scientific language more apparent than in the field of molecular machines. Much of the terminology used to describe molecular-level machines has its origins in observations made by biologists and physicists, and their findings and descriptions have often been misinterpreted and misunderstood by chemists. In 2007 we formalized definitions of some common terms used in the field (e.g., “machine”, “switch”, “motor”, “ratchet”, etc.) so that chemists could use them in a manner consistent with the meanings understood by biologists and physicists who study molecular-level machines.14

The word “machine” implies a mechanical movement that accomplishes a useful task. This Review concentrates on systems where a stimulus triggers the controlled, relatively large amplitude (or directional) motion of one molecular or submolecular component relative to another that can potentially result in a net task being performed. Molecular machines can be further categorized into various classes such as “motors” and “switches” whose behavior differs significantly.14 For example, in a rotaxane-based “switch”, the change in position of a macrocycle on the thread of the rotaxane influences the system only as a function of state. Returning the components of a molecular switch to their original position undoes any work done, and so a switch cannot be used repetitively and progressively to do work. A “motor”, on the other hand, influences a system as a function of trajectory, meaning that when the components of a molecular motor return to their original positions, for example, after a 360° directional rotation, any work that has been done is not undone unless the motor is subsequently rotated by 360° in the reverse direction. This difference in behavior is significant; no “switch-based” molecular machine can be used to progressively perform work in the way that biological motors can, such as those from the kinesin, myosin, and dynein superfamilies, unless the switch is part of a larger ratchet mechanism.14

Artificial Molecular Machines

Advances in soft robotics, materials science, and stretchable electronics have enabled rapid progress in soft grippers. Here, a critical overview of soft robotic grippers is presented, covering different material sets, physical principles, and device architectures. Soft gripping can be categorized into three technologies, enabling grasping by: a) actuation, b) controlled stiffness, and c) controlled adhesion. A comprehensive review of each type is presented. Compared to rigid grippers, end-effectors fabricated from flexible and soft components can often grasp or manipulate a larger variety of objects. Such grippers are an example of morphological computation, where control complexity is greatly reduced by material softness and mechanical compliance. Advanced materials and soft components, in particular silicone elastomers, shape memory materials, and active polymers and gels, are increasingly investigated for the design of lighter, simpler, and more universal grippers, using the inherent functionality of the materials. Embedding stretchable distributed sensors in or on soft grippers greatly enhances the ways in which the grippers interact with objects. Challenges for soft grippers include miniaturization, robustness, speed, integration of sensing, and control. Improved materials, processing methods, and sensing play an important role in future research.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adma.201707035

Soft Robotic Grippers.

DNA has become one of the most extensively used molecular building blocks for engineering self-assembling materials. DNA origami is a technique that uses hundreds of short DNA oligonucleotides, called staple strands, to fold a long single-stranded DNA, which is called a scaffold strand, into various designer nanoscale architectures. DNA origami has dramatically improved the complexity and scalability of DNA nanostructures. Due to its high degree of customization and spatial addressability, DNA origami provides a versatile platform with which to engineer nanoscale structures and devices that can sense, compute, and actuate. These capabilities open up opportunities for a broad range of applications in chemistry, biology, physics, material science, and computer science that have often required programmed spatial control of molecules and atoms in three-dimensional (3D) space. This review provides a comprehensive survey of recent developments in DNA origami structure, design, assembly, and directed self-assemb...

DNA Origami: Scaffolds for Creating Higher Order Structures

Over the past decade, we have seen rapid advances in applying nanotechnology in biomedical areas including bioimaging, biodetection, and drug delivery. As an emerging field, DNA nanotechnology offers simple yet powerful design techniques for self-assembly of nanostructures with unique advantages and high potential in enhancing drug targeting and reducing drug toxicity. Various sequence programming and optimization approaches have been developed to design DNA nanostructures with precisely engineered, controllable size, shape, surface chemistry, and function. Potent anticancer drug molecules, including Doxorubicin and CpG oligonucleotides, have been successfully loaded on DNA nanostructures to increase their cell uptake efficiency. These advances have implicated the bright future of DNA nanotechnology-enabled nanomedicine. In this review, we begin with the origin of DNA nanotechnology, followed by summarizing state-of-the-art strategies for the construction of DNA nanostructures and drug payloads delivered ...

DNA Nanotechnology-Enabled Drug Delivery Systems

DNA origami enables the precise fabrication of nanoscale geometries. We demonstrate an approach to engineer complex and reversible motion of nanoscale DNA origami machine elements. We first design, fabricate, and characterize the mechanical behavior of flexible DNA origami rotational and linear joints that integrate stiff double-stranded DNA components and flexible single-stranded DNA components to constrain motion along a single degree of freedom and demonstrate the ability to tune the flexibility and range of motion. Multiple joints with simple 1D motion were then integrated into higher order mechanisms. One mechanism is a crank–slider that couples rotational and linear motion, and the other is a Bennett linkage that moves between a compacted bundle and an expanded frame configuration with a constrained 3D motion path. Finally, we demonstrate distributed actuation of the linkage using DNA input strands to achieve reversible conformational changes of the entire structure on ∼minute timescales. Our results demonstrate programmable motion of 2D and 3D DNA origami mechanisms constructed following a macroscopic machine design approach.

https://www.pnas.org/content/pnas/112/3/713.full.pdf

Programmable motion of DNA origami mechanisms

In this paper, a pseudo-rigid-body (PRB) 3R model which consists of four rigid links joined by three revolute joints and three torsion springs is proposed for approximating the de∞ection of a cantilever beam subject to a general tip load. The large de∞ection beam equations are solved through numerical integration. A comprehensive atlas of the tip de∞ection for various load modes is obtained. A three-dimensional search routine has been developed to flnd the optimal set of characteristic radius factors and spring stifiness of the PRB 3R model. Detailed error analysis has been done by comparing with the pre-computed tip de∞ection atlas. Our results show that the approximation error is much less than that of the conventional PBR 1R model. The beneflts of the PRB 3R model include (a) load independence which is critical for analysis/synthesis applications where loads vary signiflcantly, (b) high accuracy for large de∞ection beams, and (c) explicit kinematic and static constraint equations which are simpler to solve compared with the flnite element model. To demonstrate the use of the PRB 3R model, a compliant 4-bar linkage is studied and verifled by a numerical example. The result shows a maximum tip de∞ection error of 1:2% compared with the FEA model.

A Pseudorigid-Body 3R Model for Determining Large Deflection of Cantilever Beams Subject to Tip Loads

This paper details the design and fabrication process of a fully integrated soft humanoid robotic hand with five finger that integrate an embedded shape memory alloy (SMA) actuator and a piezoelectric transducer (PZT) flexure sensor. Several challenges including precise control of the SMA actuator, improving power efficiency, and reducing actuation current and response time have been addressed. First, a Ni-Ti SMA strip is pretrained to a circular shape. Second, it is wrapped with a Ni-Cr resistance wire that is coated with thermally conductive and electrically isolating material. This design significantly reduces actuation current, improves circuit efficiency, and hence reduces response time and increases power efficiency. Third, an antagonistic SMA strip is used to improve the shape recovery rate. Fourth, the SMA actuator, the recovery SMA strip, and a flexure sensor are inserted into a 3D printed mold which is filled with silicon rubber materials. The flexure sensor feeds back the finger shape for precise control. Fifth, a demolding process yields a fully integrated multifunctional soft robotic finger. We also fabricated a hand assembled with five fingers and a palm. We measured its performance and specifications with experiments. We demonstrated its capability of grasping various kinds of regular or irregular objects. The soft robotic hand is very robust and has a large compliance, which makes it ideal for use in an unstructured environment. It is inherently safe to human operators as it can withstand large impacts and unintended contacts without causing any injury to human operators or damage to the environment.

Design and Fabrication of a Soft Robotic Hand With Embedded Actuators and Sensors

Structural DNA nanotechnology is a rapidly emerging field that has demonstrated great potential for applications such as single molecule sensing, drug delivery, and templating molecular components. As the applications of DNA nanotechnology expand, a consideration of their mechanical behavior is becoming essential to understand how these structures will respond to physical interactions. This review considers three major avenues of recent progress in this area: (1) measuring and designing mechanical properties of DNA nanostructures, (2) designing complex nanostructures based on imposed mechanical stresses, and (3) designing and controlling structurally dynamic nanostructures. This work has laid the foundation for mechanically active nanomachines that can generate, transmit, and respond to physical cues in molecular systems.

Mechanical design of DNA nanostructures

DNA origami enables fabrication of precise nanostructures by programming the self-assembly of DNA. While this approach has been used to make a variety of complex 2D and 3D objects, the mechanical functionality of these structures is limited due to their rigid nature. We explore the fabrication of deformable, or compliant, objects to establish a framework for mechanically functional nanostructures. This compliant design approach is used in macroscopic engineering to make devices including sensors, actuators, and robots. We build compliant nanostructures by utilizing the entropic elasticity of single-stranded DNA (ssDNA) to locally bend bundles of double-stranded DNA into bent geometries whose curvature and mechanical properties can be tuned by controlling the length of ssDNA strands. We demonstrate an ability to achieve a wide range of geometries by adjusting a few strands in the nanostructure design. We further developed a mechanical model to predict both geometry and mechanical properties of our compliant nanostructures that agrees well with experiments. Our results provide a basis for the design of mechanically functional DNA origami devices and materials.

Hai-Jun Su

Papers

Programmable motion of DNA origami mechanisms

A Pseudorigid-Body 3R Model for Determining Large Deflection of Cantilever Beams Subject to Tip Loads

Design and Fabrication of a Soft Robotic Hand With Embedded Actuators and Sensors

Mechanical design of DNA nanostructures

DNA origami compliant nanostructures with tunable mechanical properties.