publications
publications in reversed chronological order
2024
- Braiding, twisting, and weaving microscale fibers with capillary forcesAhmed Sherif, Maya Winters Faaborg, Cheng Zeng, Michael P. Brenner, and Vinothan N. ManoharanSoft Matter, 2024DOI: 10.1039/D3SM01732J
We present a 3D-printed machine that uses repulsive capillary forces to programmably braid, twist, and weave micrometer-scale fibers. , Soft materials made from braided or woven microscale fibers can display unique properties that can be exploited in electromagnetic, mechanical, and biomedical applications. These properties depend on the topology of the braids or weaves—that is, the order in which fibers cross one another. Current industrial braiding and weaving machines cannot easily braid or weave micrometer-scale fibers into controllable topologies; they typically apply forces that are large enough to break the fibers, and each machine can typically make only one topology. Here we use a 3D-printed device called a “capillary machine” to manipulate micrometer-scale fibers without breaking them. The operating principle is the physics of capillary forces: as the machines move vertically, they exert lateral capillary forces on floating objects, which in turn move small fibers connected to them. We present a new type of capillary machine that is based on principles of braid theory. It implements all the possible fiber-swapping operations for a set of four fibers and can therefore make any four-strand topology, including braids, twists, hierarchical twists, and weaves. We make these different topologies by changing the pattern of vertical motion of the machine. This approach is a mechanically simple, yet versatile way to make micro- and nano-textiles. We describe the prospects and limitations of this new type of machine for applications.
2022
- 3D-printed machines that manipulate microscopic objects using capillary forcesCheng Zeng, Maya Winters Faaborg, Ahmed Sherif, Martin J. Falk, Rozhin Hajian, Ming Xiao, Kara Hartig, Yohai Bar-Sinai, Michael P. Brenner, and Vinothan N. ManoharanNature, Nov 2022
Objects that deform a liquid interface are subject to capillary forces, which can be harnessed to assemble the objects. Once assembled, such structures are generally static. Here we dynamically modulate these forces to move objects in programmable two-dimensional patterns. We 3D-print devices containing channels that trap floating objects using repulsive capillary forces, then move these devices vertically in a water bath. Because the channel cross-sections vary with height, the trapped objects can be steered in two dimensions. The device and interface therefore constitute a simple machine that converts vertical to lateral motion. We design machines that translate, rotate and separate multiple floating objects and that do work on submerged objects through cyclic vertical motion. We combine these elementary machines to make centimetre-scale compound machines that braid micrometre-scale filaments into prescribed topologies, including non-repeating braids. Capillary machines are distinct from mechanical, optical or fluidic micromanipulators in that a meniscus links the object to the machine. Therefore, the channel shapes need only be controlled on the scale of the capillary length (a few millimetres), even when the objects are microscopic. Consequently, such machines can be built quickly and inexpensively. This approach could be used to manipulate micrometre-scale particles or to braid microwires for high-frequency electronics.
2021
- Virus Mechanics under Molecular CrowdingCheng Zeng, Liam Scott, Andrey Malyutin, Roya Zandi, Paul Van Der Schoot, and Bogdan DragneaThe Journal of Physical Chemistry B, Feb 2021
Viruses avoid exposure of the viral genome to harmful agents with the help of a protective protein shell known as the capsid. A secondary effect of this protective barrier is that macromolecules that may be in high concentration on the outside cannot freely diffuse across it. Therefore, inside the cell and possibly even outside, the intact virus is generally under a state of osmotic stress. Viruses deal with this type of stress in various ways. In some cases, they might harness it for infection. However, the magnitude and influence of osmotic stress on virus physical properties remains virtually unexplored for single-stranded RNA virusesthe most abundant class of viruses. Here, we report on how a model system for the positive-sense RNA icosahedral viruses, brome mosaic virus (BMV), responds to osmotic pressure. Specifically, we study the mechanical properties and structural stability of BMV under controlled molecular crowding conditions. We show that BMV is mechanically reinforced under a small external osmotic pressure but starts to yield after a threshold pressure is reached. We explain this mechanochemical behavior as an effect of the molecular crowding on the entropy of the “breathing” fluctuation modes of the virus shell. The experimental results are consistent with the viral RNA imposing a small negative internal osmotic pressure that prestresses the capsid. Our findings add a new line of inquiry to be considered when addressing the mechanisms of viral disassembly inside the crowded environment of the cell.
2019
- Intermittency of Deformation and the Elastic Limit of an Icosahedral Virus under CompressionMercedes Hernando-Pérez, Cheng Zeng, M. Carmen Miguel, and Bogdan DragneaACS Nano, Jul 2019
Viruses undergo mesoscopic morphological changes as they interact with host interfaces and in response to chemical cues. The dynamics of these changes, over the entire temporal range relevant to virus processes, are unclear. Here, we report on creep compliance experiments on a small icosahedral virus under uniaxial constant stress. We find that even at small stresses, well below the yielding point and generally thought to induce a Hookean response, strain continues to develop in time via sparse, randomly distributed, relatively rapid plastic events. The intermittent character of mechanical compliance only appears above a loading threshold, similar to situations encountered in granular flows and the plastic deformation of crystalline solids. The threshold load is much smaller for the empty capsids of the brome mosaic virus than for the wild-type virions. The difference highlights the involvement of RNA in stabilizing the assembly interface. Numerical simulations of spherical crystal deformation suggest intermittency is mediated by lattice defect dynamics and identify the type of compression-induced defect that nucleates the transition to plasticity.
2018
- Defects and Chirality in the Nanoparticle-Directed Assembly of Spherocylindrical Shells of Virus Coat ProteinsCheng Zeng, Guillermo Rodriguez Lázaro, Irina B. Tsvetkova, Michael F. Hagan, and Bogdan DragneaACS Nano, Jun 2018
Virus coat proteins of small isometric plant viruses readily assemble into symmetric, icosahedral cages encapsulating noncognate cargo, provided the cargo meets a minimal set of chemical and physical requirements. While this capability has been intensely explored for certain virus-enabled nanotechnologies, additional applications require lower symmetry than that of an icosahedron. Here, we show that the coat proteins of an icosahedral virus can efficiently assemble around metal nanorods into spherocylindrical closed shells with hexagonally close-packed bodies and icosahedral caps. Comparison of chiral angles and packing defects observed by in situ atomic force microscopy with those obtained from molecular dynamics models offers insight into the mechanism of growth, and the influence of stresses associated with intrinsic curvature and assembly pathways.
2017
- In Situ Atomic Force Microscopy Studies on Nucleation and Self-Assembly of Biogenic and Bio-Inspired MaterialsCheng Zeng, Caitlin Vitale-Sullivan, and Xiang MaMinerals, Aug 2017DOI: 10.3390/min7090158
Through billions of years of evolution, nature has been able to create highly sophisticated and ordered structures in living systems, including cells, cellular components and viruses. The formation of these structures involves nucleation and self-assembly, which are fundamental physical processes associated with the formation of any ordered structure. It is important to understand how biogenic materials self-assemble into functional and highly ordered structures in order to determine the mechanisms of biological systems, as well as design and produce new classes of materials which are inspired by nature but equipped with better physiochemical properties for our purposes. An ideal tool for the study of nucleation and self-assembly is in situ atomic force microscopy (AFM), which has been widely used in this field and further developed for different applications in recent years. The main aim of this work is to review the latest contributions that have been reported on studies of nucleation and self-assembly of biogenic and bio-inspired materials using in situ AFM. We will address this topic by introducing the background of AFM, and discussing recent in situ AFM studies on nucleation and self-assembly of soft biogenic, soft bioinspired and hard materials.
- Probing the Link among Genomic Cargo, Contact Mechanics, and Nanoindentation in Recombinant Adeno-Associated Virus 2Cheng Zeng, Sven Moller-Tank, Aravind Asokan, and Bogdan DragneaThe Journal of Physical Chemistry B, Mar 2017
Recombinant adeno-associated virus (AAV) is a promising gene therapy vector. To make progress in this direction, the relationship between the characteristics of the genomic cargo and the capsid stability must be understood in detail. The goal of this study is to determine the role of the packaged vector genome in the response of AAV particles to mechanical compression and adhesion to a substrate. Specifically, we used atomic force microscopy to compare the mechanical properties of empty AAV serotype 2 (AAV2) capsids and AAV2 vectors packaging single-stranded DNA or self-complementary DNA. We found that all species underwent partial deformation upon adsorption from buffer on an atomically flat graphite surface. Upon adsorption, a preferred orientation toward the twofold symmetry axis on the capsid, relative to the substrate, was observed. The magnitude of the bias depended on the cargo type, indicating that the interfacial properties may be influenced by cargo. All particles showed a significant relative strain before rupture. Different from interfacial interactions, which were clearly cargo-dependent, the elastic response to directional stress was largely dominated by the capsid properties. Nevertheless, small differences between particles laden with different cargo were measurable; scAAV vectors were the most resilient to external compression. We also show how elastic constant and rupture force data sets can be analyzed according a multivariate conditional probability approach to determine the genome content on the basis of a database of mechanical properties acquired from nanoindentation assays. Implications for understanding how recombinant AAV capsid−genome interactions can affect vector stability and effectiveness of gene therapy applications are discussed.
- Contact Mechanics of a Small Icosahedral VirusCheng Zeng, Mercedes Hernando-Pérez, Bogdan Dragnea, Xiang Ma, Paul Schoot, and Roya ZandiPhysical Review Letters, Jul 2017
A virus binding to a surface causes stress of the virus cage near the contact area. Here, we investigate the potential role of substrate-induced structural perturbation in the mechanical response of virus particles to adsorption. This is particularly relevant to the broad category of viruses stabilized by weak noncovalent interactions. We utilize atomic force microscopy to measure height distributions of the brome mosaic virus upon adsorption from solution on atomically flat substrates and present a continuum model that captures our observations and provides estimates of elastic properties and of the interfacial energy of the virus, without recourse to indentation.
- Structure and mechanochemistry of icosahedral viruses and virus shells studied by atomic force microscopyCheng ZengJul 2017ISBN: 978-1-369-59398-3 Publication Title: ProQuest Dissertations and Theses 10257038
Viruses are ubiquitous biological entities that have been increasingly adopted for positive applications. Fundamental knowledge of virus structure and stabilities is vital for understanding virus infection and development of novel virus-based materials. During an infectious cycle, the viral capsid has to pass through numerous cellular barriers and simultaneously encounter forces. Thus, it is important to understand how virus capsids react to mechanical perturbations. This dissertation work takes on the structure and mechanochemistry of icosahedral viruses and virus shells. Atomic force microscopy (AFM) imaging and nano-indentation are the primary methods utilized in this study because they provide good spatial and force resolution for understanding the nano-mechanical events. The types of strain that were examined include compression, flattening, shrinkage, collapse, etc. Firstly, we studied the adsorption of viruses on AFM substrates to understand the impact of adhesive interactions. We have discovered an orientation bias and a surface-induced deformation upon adsorption. A physical model was also proposed to describe the mechanochemical properties of the capsid without performing indentation. Secondly, an AFM nano-indentation assay in presence of macromolecules was carried out to mimic crowding effect. A small external osmotic pressure was found to stiffen the capsid, while higher osmotic pressure can soften the capsid. Thirdly, the resilience of virus capsids was studied by dehydration and nano-indentation. We observed a remarkable recovery of capsid after a dehydration/rehydration cycle. Plastic deformation was observed for BMV after deep indentation. Fourthly, the capsomeric structure of virus-like particles (VLPs) was determined for the first time for both spherical and spherocylindrical particles. Structural analyses were performed to understand the origin of defects as well. Lastly, the surface adsorption and elasticity was examined for a gene therapy vector. Connections were found between mechanochemical properties and encapsulated cargo. A statistical model was put forward for prediction of cargo type.
2016
- Nanoindentation of Isometric Viruses on Deterministically Corrugated SubstratesM. Hernando-Pérez, Cheng Zeng, L. Delalande, I.B. Tsvetkova, A. Bousquet, M. Tayachi-Pigeonnat, R. Temam, and B. DragneaThe Journal of Physical Chemistry B, Jan 2016
It has been just over 100 years since inventor Joseph Coyle perfected the egg cartona package format that has known very little changes since its first appearance (Dhillon, S. B. C. Inventor Created Better Way to Carry Eggs. In The Globe and Mail Vancouver, 2013). In this article, we extend Coyle’s old idea to the study of mechanical properties of viruses. Virus stiffness, strength, and breaking force obtained by force spectroscopy atomic force microscopy (AFM) provide the knowledge required for designing nanocontainers for applications in biotechnology and medicine, and for understanding the fundamentals of virus−host interaction such as virus translocation from one cellular compartment to another. In previous studies, virus particles adsorbed on flat surfaces from a physiological buffer were subjected to directional deformation by a known force exerted via a microscopic probe. The affinity between the virus shell and surface is required to be strong enough to anchor particles on the substrate while they are indented or imaged, yet sufficiently weak to preserve the native structure and interactions prior deformation. The specific question addressed here is whether an experimental scheme characterized by increased contact area and stable mechanical equilibrium under directional compression would provide a more reliable characterization than the traditional flat substrate approach.
- Catching a virus in a molecular netL. Delalande, I. B. Tsvetkova, Cheng Zeng, K. Bond, M. F. Jarrold, and B. DragneaNanoscale, Jan 2016DOI: 10.1039/C6NR04469G
A metal–organic molecular net composed of tannic acid (TA) and iron(III) was constructed around the brome mosaic virus (BMV) particle to determine whether the added net could act as a transport barrier for water, and if the net could stabilize the virus in physically or chemically challenging environments. This new virus engineering strategy is expected to provide benefits both in the study and technological applications of viruses. For instance, a virus wrapped in a thin molecular layer could be extracted from solution either in air or vacuum, and its structure, composition and even internal dynamics could be interrogated by methods not compatible with a liquid environment. Atomic force microscopy (AFM) studies of Fe(III)–TA coated BMV in liquid and in air supported a marked resistance to dehydration when compared to wtBMV. Native charge detection mass spectrometry (CDMS), was employed to estimate the number of molecules in the molecular net which wrapped the virus. The CDMS data suggested that less than one molecular monolayer wrapped the virus. Additionally, it was found, that this very thin molecular coat was sufficient to render the coated viruses resistant to storage conditions that typically lead to virus disassembly over time. A temporary coat imparting increased resistance to disassembly could be useful in adding time delay control or alleviate required storage conditions of engineered viruses for therapeutic purposes.