Do we understand the mechanisms used by biological systems to
correct their errors?
This
paper is a review of kinetic proofreading in biological systems, presented in a
mostly historical fashion. The original concept of kinetic proofreading as
introduced by Hopfield and Ninio is recounted. Following this, the concept of
trade-offs between speed, energy dissipation and accuracy is introduced. The
key results that biological systems tend to get accuracy to within acceptable
levels, then prioritise maximising speed, followed by minimising energy
dissipation is presented. In the process of explaining this, a number of
methods utilised are briefly mentioned including: first passage time analysis,
asymptotic analysis, and thermodynamic uncertainty relations. Finally, the
concept of energetic vs kinetic discrimination is briefly introduced.
https://pubs.acs.org/doi/10.1021/acs.jpcb.0c06180
A
biomimetic DNA‐based membrane gate for protein‐controlled transport of
cytotoxic drugs
The
ability to design membrane nanopores with controllable channel opening has the
potential to have many applications in biomedicine, biosensing and artificial
cells. In this paper, the researchers have shown the design and synthesis of a
membrane nanopore constructed of only seven oligonucleotides where the lid of
the nanopore is a thrombin/binding aptamer (TBA). Therefore, passage of small
molecules through the nanopore is only allowed in presence of thrombin. It is
shown that the nanopores can be incorporated in lipid vesicles.
Nanopore-incorporated vesicles containing fluorescent dye are observed to
release the dye only in presence of thrombin which proves that the channel
opening is tightly controlled. This approach is applied to release biologically
relevant molecules for controlled killing of cells. Cytotoxic drug topotecan is
filled in vesicles containing the nanopores on the membrane; and these vesicles
are added to HeLa cervical cancer cells. Upon addition of thrombin, the drug is
released to the cells, and cell viability drops to 20% after three days
compared to 95% when no thrombin is added. This paper thus shows a simple
approach for biocompatible membrane nanopore design which can be opened by the
presence of a biologically relevant substance.
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202011583
DNA
origami guided self-assembly of plasmonic polymers with robust long-range
plasmonic resonance
The production
of 1D chains by assembling DNA origami tiles have been widely used in
nanofabrication. The defined geometry of the DNA tiles is harnessed to control
the distance between DNA-bound metallic nanoparticles, producing nanowires used
for plasmon propagation. However, regular origami tile assemblies are flawed by
its flexibility, which leads to defects in plasmon signal propagation due to
the variable distance between nanoparticles. The authors of this paper optimise
the rigidity of the DNA origami chains by exchanging the classical tile for a
hashtag-shaped structure. The proposed hashtag-structure can be functionalised
with nanoparticles in several ways, while increasing the persistence length of
the produced nanowires by one order of magnitude.
https://pubs.acs.org/doi/abs/10.1021/acs.nanolett.0c04055
Combinatorial
signal perception in the BMP pathway
Cells
can sense ligands in their environment which bind to receptors on their
surface, and trigger a response through intra-cellular signalling pathways.
There are many types of type 1 and type 2 receptors in the bone morphogen
pathway (BMP) that a cell could express, even more types of dimeric ligands
that could be sensed. Through a combination of an in vivo search and
the construction of a minimal mathematical model, Antebi et al. create a
framework through which we can understand the multifarious signal processing
operations that occur at the boundaries of cells. Crucially, the concentration
of ligands (which is assumed to greatly exceed the number of available
receptors) and the affinities between receptors and ligands determine the
equilibrium distribution of ligand-receptor configurations, but the activity
(the strength with which a ligand receptor combo can catalyse a signal) of the
configuration does not need correlate with its probability of occurrence.
Therefore, in a system with two types of surface receptors and two types of
ligands (each with an affinity and activity with each receptor), the signal
transduced can quantitatively differ when the ligands are presented alone or in
combination.
https://doi.org/10.1016/j.cell.2017.08.015
3D engine in DNA code
Turing-completeness of Chemical Reaction Networks as well as the
capability to be mapped into DNA Strand Displacement systems is always brought
up as a proof of their versatility. However, most of the academic literature
focuses on the implementation of CRNs in the context of building controllers,
cellular automata or other sorts of computer science model problems rather than
software applications that are found in our daily life. The present work
presents how to encode a rudimentary 3D shader engine into a CRN and how to
emulate and execute it, the most interesting part being how does it display a
mapping between a high level standard abstraction language (Like JavaScript and
CRNs). While still being impractical when compared to silicon-based devices,
it's easy to see how a bridge between regular coding skills and molecular
programming can be built. But it also must be said that in terms of software
conservation, being able to engineer a sort of CRN/DNA-based assembler code
that an be retroengineered into a high level language can be a promising
technology to preserve software in a format with a longer life than optical or
magnetic devices.
https://observablehq.com/@pallada-92/3d-engine-in-dna-code
Computing signal transduction in signaling networks modeled as
Boolean Networks, Petri Nets and hypergraphs
Transduction networks are known for being the regular architecture
used bicellular systems to perform signal processing and decision making. Back
from the foundational work by Dennis Bray they have been described as
distributed network computing elements and mappings with computational models
(mainly neural networks) have been drawn. But alternative mappings with other
computing models can be drawn. In this paper, the authors explore other
networks computing models that can be used to model transduction such as
graphs, hypergraphs, Boolean Networks or Petri Nets, establishing the
conditions in which a model is isomorphic to another and highlighting the
strengths and weaknesses of each one. However, some of the strengths attributed
to the Boolean Network model are rarely found in a biological context and none
of the models take into account explicitly the catalytic nature of the network
elements and the implications of the system, thus leaving room to potential new
formalisms.
https://www.biorxiv.org/content/10.1101/272344v2.full
Self-limiting
polymerization of DNA origami subunits with strain accumulation
The polymerization of DNA origami was controlled by accumulated
strain during the growth process. The DNA origami consist of three domains with
the middle domain being shorter than others. As the three domains are connected
by linkers, they can deform while they grow, accumulating the strain coming
from short middle domain. By controlling the length of the middle domain, the
authors precisely controlled the growth of the DNA origami objects without any
external control.
https://pubs.acs.org/doi/10.1021/acsnano.0c07696
Single
cell characterization of a synthetic bacterial clock with a hybrid feedback
loop containing dCas9-sgRNA
Oscillatory
dynamics facilitates the temporal orchestration of metabolic and growth
processes inside cells and organisms. In this work, they present a synthetic
oscillator gene circuit (repressilator) in which one of the repressors was
replaced by CRISPRi system and they monitored the oscillations in microfluidic
reacts using single cell experiments. They found that the period of the
oscillator is much slower since it depends on the irreversible binding of the
CRISPR system that prolongs its dilution phase. They propose to use RNA
aptamers and use CRISPRa (activation) to improve the dynamics of the oscillator
and explore the potential applications.
https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00438
A ratiometric electrochemical biosensor for the exosomal
microRNAs detection based on bipedal DNA walkers propelled by locked nucleic
acid modified toehold mediate strand displacement reaction
In this paper, the researchers attempted to develop a novel
biosensor for exosomal miRNAs, which achieved high sensitivity, high
specificity and high reproducibility, such that the biosensor could be used
multiple times. Their system involved locked nucleic acid capture probe
associated with a bipedal DNA walker. The presence of the target miRNA led to
release of the bipedal DNA walker by toehold-mediated strand displacement. The
DNA walker walking over the electrode surface facilitated amplification of the
electrochemical signal, allowing a low signal-to-background ratio.
https://www.sciencedirect.com/science/article/pii/S0956566317307170
Reciprocal coupling in
chemically fueled assembly: A reaction cycle regulates self-assembly and vice
versa
The authors seek to develop a synthetic system that replicates the
behaviour of natural biopolymers such as actin, in which the constituent
monomers can adopt two states, one of which is favourable for polymerisation
("active") and the other of which is less so. Moreover, the
environment of the polymer catalyses the deactivation of the monomers, leading
to non-equilibrium "living" polymerisation. The resultant dynamics
are essential to cytoskeletal mechanics and motion. In this paper, the
assembling monomers are short peptides with a switachble chemical moiety which
can be charged (inactive) or neutral (active). Differential assembly in the two
regimes is demonstrated, as is a catalytic effect on activation/deactivation
rates of the polymer environment. However, the paper doesn't demonstrate
preferential deactivation in the polymer state, as is seen in the natural
counterpart.
https://pubs.acs.org/doi/10.1021/jacs.0c10486
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