Universal computing by DNA origami robots in a living animal

Biological systems are collections of discrete molecular objects that move around and collide with each other. Cells carry out elaborate processes by precisely controlling these collisions, but developing artificial machines that can interface with and control such interactions remains a significant challenge. DNA is a natural substrate for computing and has been used to implement a diverse set of mathematical problems1-3, logic circuits4-6 and robotics7-9. The molecule also naturally interfaces with living systems, and different forms of DNA-based biocomputing have previously been demonstrated10-13. Here we show that DNA origami14-16 can be used to fabricate nanoscale robots that are capable of dynamically interacting with each other17-18 in a living animal. The interactions generate logical outputs, which are relayed to switch molecular payloads on or off. As a proof-of-principle, we use the system to create architectures that emulate various logic gates (AND, OR, XOR, NAND, NOT, CNOT, and a half adder). Following an ex vivo prototyping phase, we successfully employed the DNA origami robots in living cockroaches (Blaberus discoidalis) to control a molecule that targets the cells of the animal

Topology optimization of rigid interlocking assemblies

This paper presents a new density-based topology optimization algorithm for the design of constructible rigid interlocking assemblies with multiple components. The multiple components or structural parts are introduced by having multiple sets of design variables: one for each component. These are filtered separately and combined to create a density field for each structural part. In addition, the framework uses a series of filtering operations to ensure sufficient blocking of rigid body motion and sufficient assemblability. Since this type of assembly is frequently constructed both with and without the use of mortars or adhesives, the structural performance is simplified into a set of static load cases in which the inter-component interactions are estimated. The framework is demonstrated on design examples with two and four components and found to achieve interlocking, constructible assemblies. Crisp interface boundaries and interaction loads along the component interfaces are observed for all examples. Additionally, the two-component solutions are analyzed and compared using computational contact analyses to investigate the influence of the user defined parameters. Finally, an extension is suggested that allows the inclusion of a void phase

Apoptotic dysregulation mediates stem cell competition and tissue regeneration

Abstract Since adult stem cells are responsible for replenishing tissues throughout life, it is vital to understand how failure to undergo apoptosis can dictate stem cell behavior both intrinsically and non-autonomously. Here, we report that depletion of pro-apoptotic Bax protein bestows hair follicle stem cells with the capacity to eliminate viable neighboring cells by sequestration of TNFα in their membrane. This in turn induces apoptosis in “loser” cells in a contact-dependent manner. Examining the underlying mechanism, we find that Bax loss-of-function competitive phenotype is mediated by the intrinsic activation of NFκB. Notably, winner stem cells differentially respond to TNFα, owing to their elevated expression of TNFR2. Finally, we report that in vivo depletion of Bax results in an increased stem cell pool, accelerating wound-repair and de novo hair follicle regeneration. Collectively, we establish a mechanism of mammalian cell competition, which can have broad therapeutic implications for tissue regeneration and tumorigenesis

A symbiotic-like biologically-driven regenerating fabric

Living organisms constantly maintain their structural and biochemical integrity by the critical means of response, healing, and regeneration. Inanimate objects, on the other hand, are axiomatically considered incapable of responding to damage and healing it, leading to the profound negative environmental impact of their continuous manufacturing and trashing. Objects with such biological properties would be a significant step towards sustainable technology. In this work we present a feasible strategy for driving regeneration in fabric by means of integration with a bacterial biofilm to obtain a symbiotic-like hybrid - the fabric provides structural framework to the biofilm and supports its growth, whereas the biofilm responds to mechanical tear by synthesizing a silk protein engineered to self-assemble upon secretion from the cells. We propose the term crossbiosis to describe this and other hybrid systems combining organism and object. Our strategy could be implemented in other systems and drive sensing of integrity and response by regeneration in other materials as well

Design principles of biologically fabricated avian nests

Abstract Materials and construction methods of nests vary between bird species and at present, very little is known about the relationships between architecture and function in these structures. This study combines computational and experimental techniques to study the structural biology of nests fabricated by the edible nest swiftlet Aerodramus fuciphagus on vertical rock walls using threaded saliva. Utilizing its own saliva as a construction material allows the swiftlets full control over the structural features at a very high resolution in a process similar to additive manufacturing. It was hypothesized that the mechanical properties would vary between the structural regions of the nest (i.e. anchoring to the wall, center of the cup, and rim) mainly by means of architecture to offer structural support and bear the natural loads of birds and eggs. We generated numerical models of swiftlet nests from μCT scans based on collected swiftlet nests, which we loaded with a force of birds and eggs. This was done in order to study and assess the stress distribution that characterizes the specific nest’s architecture, evaluate its strength and weak points if any, as well as to understand the rationale and benefits that underlie this natural structure. We show that macro- and micro-scale structural patterns are identical in all nests, suggesting that their construction is governed by specific design principles. The nests’ response to applied loads of birds and eggs in finite element simulations suggests a mechanical overdesign strategy, which ensures the stresses experienced by its components in any loading scenario are actively minimized to be significantly smaller than the tensile fracture strength of the nests’ material. These findings highlight mechanical overdesign as a biological strategy for resilient, single-material constructions designed to protect eggs and hatchlings