Interface Focus

[This corrects the article DOI: 10.1098/rsfs.2022.0048.][This corrects the article DOI: 10.1098/rsfs.2022.0048.].

Fibrosis has been mechanistically linked to arrhythmogenesis in multiple cardiovascular conditions, including atrial fibrillation (AF). Previous studies have demonstrated that fibrosis can create functional barriers to conduction which may promote excitation wavebreak and the generation of re-entry, while also acting to pin re-entrant excitation in stable rotors during AF. However, few studies have investigated the role of fibrosis in the generation of AF triggers in detail. We apply our in-house computational framework to study the impact of fibrosis on the generation of AF triggers and trigger-substrate interactions in two- and three-dimensional atrial tissue models...

Persistent atrial fibrillation (AF) is not effectively treated due to a lack of adequate tools for identifying patient-specific AF substrates. Recent studies revealed that in 30-50% of patients, persistent AF is maintained by localized drivers not only in the left atrium (LA) but also in the right atrium (RA). The chamber-specific atrial wall thickness (AWT) features underlying AF remain elusive, though the important role of AWT in AF is widely acknowledged. We aimed to provide direct evidence of the existence of distinguished RA and LA AWT features underlying AF drivers by analysing functionally and structurally mapped human hearts ex vivo ...

The development and bottom-up assembly of synthetic cells with a functional cytoskeleton sets a major milestone to understand cell mechanics and to develop man-made machines on the nano- and microscale. However, natural cytoskeletal components can be difficult to purify, deliberately engineer and reconstitute within synthetic cells which therefore limits the realization of multifaceted functions of modern cytoskeletons in synthetic cells. Here, we review recent progress in the development of synthetic cytoskeletons made from deoxyribonucleic acid (DNA) as a complementary strategy...

Living cells regulate many of their vital functions through dynamic, membraneless compartments that phase separate (condense) in response to different types of stimuli. In synthetic cells, responsive condensates could similarly play a crucial role in sustaining their operations. Here we use DNA nanotechnology to design and characterize artificial condensates that respond to light. These condensates form via the programmable interactions of star-shaped DNA subunits (nanostars), which are engineered to include photo-responsive protection domains...

Is it possible to build life? More specifically, is it possible to create a living synthetic cell from inanimate building blocks? This question precipitated into one of the most significant grand challenges in biochemistry and synthetic biology, with several large research consortia forming around this endeavour in Europe (European Synthetic Cell Initiative), the USA (Build-a-Cell Initiative) and Japan (Japanese Society for Cell Synthesis Research). The mature field of biochemistry, the advent of synthetic biology in the early 2000s, and the burgeoning field of cell-free synthetic biology made it feasible to tackle this grand challenge...

Construction of artificial cells requires the development of straightforward methods for mimicking natural phospholipid membrane formation. Here we describe the use of direct aminolysis ligations to spontaneously generate biomimetic phospholipid membranes from water-soluble starting materials. Additionally, we explore the suitability of such biomimetic approaches for driving the in situ formation of native phospholipid membranes. Our studies suggest that non-enzymatic ligation reactions could have been important for the synthesis of phospholipid-like membranes during the origin of life, and might be harnessed as simplified methods to enable the generation of lipid compartments in artificial cells...

No abstract text is available yet for this article.

Toehold-mediated strand displacement (TMSD) is a widely used process in dynamic DNA nanotechnology, which has been applied for the actuation of molecular devices, in biosensor applications, and for DNA-based molecular computation. Similar processes also occur in a biological context, when RNA strands invade secondary structures or duplexes of other RNA or DNA molecules. Complex reaction environments-inside cells or synthetic cells-potentially contain a large number of competing nucleic acid molecules that transiently bind to the components of the strand displacement reaction of interest and thus slow down its kinetics...

Cellular communication is a fundamental feature to ensure the survival of cellular assemblies, such as multicellular tissue, via coordinated adaption to changes in their surroundings. Consequently, the development of integrated semi-synthetic systems consisting of artificial cells (ACs) and mammalian cells requires feedback-based interactions. Here, we illustrate that ACs can eavesdrop on HepG2 cells focusing on the activity of cytochrome P450 1A2 (CYP1A2), an enzyme from the cytochrome P450 enzyme family. Specifically, d-cysteine is sent as a signal from the ACs via the triggered reduction of disulfide bonds...

Living systems are molecular assemblies whose dynamics are maintained by non-equilibrium chemical reactions. To date, artificial cells have been studied from such physical and chemical viewpoints. This review briefly gives a perspective on using DNA droplets in constructing artificial cells. A DNA droplet is a coacervate composed of DNA nanostructures, a novel category of synthetic DNA self-assembled systems. The DNA droplets have programmability in physical properties based on DNA base sequence design. The aspect of DNA as an information molecule allows physical and chemical control of nanostructure formation, molecular assembly and molecular reactions through the design of DNA base pairing...

Both deterministic and stochastic forces shape biofilm communities, but the balance between those forces is variable. Quantifying the balance is both desirable and challenging. For example, drift-driven failure, a stochastic force, can be thought of as an organism experiencing 'bad luck' and manipulating 'luck' as a factor in real-world systems is difficult. We used an agent-based model to manipulate luck by controlling seed cevalues governing random number generation. We determined which organism among identical competitors experienced the greatest drift-driven failure, gave it a deterministic growth advantage and re-ran the simulation with the same seed...

Hypothesis and theory-based studies in microbial ecology have been neglected in favour of those that are descriptive and aim for data-gathering of uncultured microbial species. This tendency limits our capacity to create new mechanistic explanations of microbial community dynamics, hampering the improvement of current environmental biotechnologies. We propose that a multiscale modelling bottom-up approach (piecing together sub-systems to give rise to more complex systems) can be used as a framework to generate mechanistic hypotheses and theories ( in-silico bottom-up methodology)...

Combining engineering and biology surely must be a route to delivering solutions to the world's most pressing problems in depleting resources, energy and the environment. Engineers and biologists have long recognized the power in coupling their disciplines and have evolved a healthy variety of approaches to realizing technologies. Yet recently, there has been a movement to narrow the remit of engineering biology. Its definition as 'the application of engineering principles to the design of biological systems' ought to encompass a broad church...

A heterotrophic-specialist model was proposed previously to divide wastewater treatment plant (WWTP) heterotrophs into sub-guilds of consumers of readily or slowly degradable substrates (RDS or SDS, respectively). The substrate degradation rate model coupled to metabolic considerations predicted that RNA and polyhydroxyalkanoate (PHA) levels would be positively correlated in the activated sludge communities with high RNA and PHA occurring in RDS-consumers, and low RNA with no PHA accumulation occurring in SDS-consumers because their external substrates are always present...

Engineered ecosystems span multiple volume scales, from a nano-scale to thousands of cubic metres. Even the largest industrial systems are tested in pilot scale facilities. But does scale affect outcomes? Here we look at comparing different size laboratory anaerobic fermentors to see if and how the volume of the community affects the outcome of community coalescence (combining multiple communities) on community composition and function. Our results show that there is an effect of scale on biogas production...

High-throughput 16S rRNA gene amplicon sequencing technology is widely applied for environmental microbiota structure analysis to derive knowledge that informs microbiome-based surveillance and oriented bioengineering. However, it remains elusive how the selection of 16S rRNA gene hypervariable regions and reference databases affects microbiota diversity and structure profiling. This study systematically evaluated the fitness of different frequently used reference databases (i.e. SILVA 138 SSU, GTDB bact120_r207, Greengenes 13_5 and MiDAS 4...

The aim of this paper is to introduce a field of study that has emerged over the last decade, called Bayesian mechanics. Bayesian mechanics is a probabilistic mechanics, comprising tools that enable us to model systems endowed with a particular partition (i.e. into particles), where the internal states (or the trajectories of internal states) of a particular system encode the parameters of beliefs about external states (or their trajectories). These tools allow us to write down mechanical theories for systems that look as if they are estimating posterior probability distributions over the causes of their sensory states...

We present a scenario for the origin of biological coding, a semiotic relationship between chemical information stored in one location that links to chemical information stored in a separate location. Coding originated from cooperation between two, originally separate, collectively autocatalytic sets (CASs), one for nucleic acids and one for peptides. Upon interaction, a series of RNA folding-directed processes led to their joint cooperativity. The aminoacyl adenylate was the first covalent association made by these two CASs and solidified their interdependence, and is a palimpsest of this era, a relic of the original semiotic relationship between RNA and proteins...

Complex living agents consist of cells, which are themselves competent sub-agents navigating physiological and metabolic spaces. Behaviour science, evolutionary developmental biology and the field of machine intelligence all seek to understand the scaling of biological cognition: what enables individual cells to integrate their activities to result in the emergence of a novel, higher-level intelligence with large-scale goals and competencies that belong to it and not to its parts? Here, we report the results of simulations based on the TAME framework, which proposes that evolution pivoted the collective intelligence of cells during morphogenesis of the body into traditional behavioural intelligence by scaling up homeostatic competencies of cells in metabolic space...