63 research outputs found
Non-Equilibrium Living Polymers
Systems of "living" polymers are ubiquitous in industry and are traditionally
realised using surfactants. Here I review the state-of-the-art of living
polymers and discuss non-equilibrium extensions that may be realised with
advanced synthetic chemistry or DNA functionalised by proteins. These systems
are not only interesting in order to realise novel "living" soft matter but can
also shed insight into how genomes are (topologically) regulated in vivo.Comment: 6 pages, 4 figure
Topological patterns in two-dimensional gel electrophoresis of DNA knots
Gel electrophoresis is a powerful experimental method to probe the
topology of DNA and other biopolymers. While there is a large
body of experimental work which allows us to accurately separate
different topoisomers of a molecule, a full theoretical understanding
of these experiments has not yet been achieved. Here we show
that the mobility of DNA knots depends crucially and subtly on
the physical properties of the gel, and in particular on the presence
of dangling ends. The topological interactions between these
and DNA molecules can be described in terms of an “entanglement
number”, and yield a non-monotonic mobility at moderate fields.
Consequently, in two-dimensional electrophoresis, gel bands display
a characteristic arc pattern; this turns into a straight line when the
density of dangling ends vanishes. We also provide a novel framework
to accurately predict the shape of such arcs as a function of
molecule length and topological complexity, which may be used to
inform future experiments
Simplifying Topological Entanglements by Entropic Competition of Slip-Links
Topological entanglements are abundant, and often detrimental, in polymeric
systems in biology and materials science. Here we theoretically investigate the
topological simplification of knots by diffusing slip-links (SLs), which may
represent biological or synthetic molecules, such as proteins on the genome or
cyclodextrines in slide-ring gels. We find that SLs entropically compete with
knots and can localise them, greatly facilitating their downstream
simplification by transient strand-crossing. We further show that the
efficiency of knot localisation strongly depends on the topology of the SL
network and, informed by our findings, discuss potential strategies to control
the topology of biological and synthetic materials
Competition between local erasure and long-range spreading of a single biochemical mark leads to epigenetic bistability
The mechanism through which cells determine their fate is intimately related
to the spreading of certain biochemical (so-called epigenetic) marks along
their genome. The mechanisms behind mark spreading and maintenance are not yet
fully understood, and current models often assume a long-range infection-like
process for the dynamics of marks, due to the polymeric nature of the chromatin
fibre which allows looping between distant sites. While these existing models
typically consider antagonising marks, here we propose a qualitatively
different scenario which analyses the spreading of a single mark. We define a
1D stochastic model in which mark spreading/infection occurs as a long-range
process whereas mark erasure/recovery is a local process, with an enhanced rate
at boundaries of infected domains. In the limiting case where our model
exhibits absorbing states, we find a first-order-like transition separating the
marked/infected phase from the unmarked/recovered phase. This suggests that our
model, in this limit, belongs to the long-range compact directed percolation
universality class. The abrupt nature of the transition is retained in a more
biophysically realistic situation when a basal infection/recovery rate is
introduced (thereby removing absorbing states). Close to the transition there
is a range of bistability where both the marked/infected and unmarked/recovered
states are metastable and long lived, which provides a possible avenue for
controlling fate decisions in cells. Increasing the basal infection/recovery
rate, we find a second transition between a coherent (marked or unmarked)
phase, and a mixed, or random, one.Comment: 11 pages, 7 figures, 2 appendice
Three-Dimensional Loop Extrusion
Loop extrusion convincingly describes how certain Structural Maintenance of
Chromosome (SMC) proteins mediate the formation of large DNA loops. Yet, most
of the existing computational models cannot reconcile recent in vitro
observations showing that condensins can traverse each other, bypass large
roadblocks and perform steps longer than its own size. To fill this gap, we
propose a three-dimensional (3D) "trans-grabbing" model for loop extrusion
which not only reproduces the experimental features of loop extrusion by one
SMC complex, but also predicts the formation of so-called "Z-loops" via the
interaction of two or more SMCs extruding along the same DNA substrate. By
performing Molecular Dynamics simulations of this model we discover that the
experimentally observed asymmetry in the different types of Z-loops is a
natural consequence of the DNA tethering in vitro. Intriguingly, our model
predicts this bias to disappear in absence of tethering and a third type of
Z-loop, which has not yet been identified in experiments, to appear. Our model
naturally explains road-block bypassing and the appearance of steps larger than
the SMC size as a consequence of non-contiguous DNA grabbing. Finally, it is
the first to our knowledge to address how Z-loops and bypassing might occur in
a way that is broadly consistent with existing cis-only 1D loop extrusion
models.Comment: to appear in biophysical journa
Loops are Geometric Catalysts for DNA Integration
The insertion of HIV and other DNA elements within genomes underpins both
genetic diversity and disease when unregulated. Most of these insertions are
not random and occupy specific positions within the genome but the physical
mechanisms underlying the integration site selection are poorly understood.
Here we perform Molecular Dynamics simulations to study the insertion of DNA
elements, such as HIV viral DNA or transposons, into naked DNA or chromatin
substrate. More specifically, we explore the role of loops in the DNA substrate
and discover that they act as "geometric catalysts" for DNA integration.
Additionally, we discover that the 1D and 3D clustering of loops affects the
distribution of integration sites. Finally, we show that loops may compete with
nucleosomes at attracting DNA integrations. These results may be tested in
vitro and they may help to understand patterns of DNA insertions with
implications in genome evolution and gene therapy
Effects of Monovalent and Divalent Cations on the Rheology of Entangled DNA
In this paper we investigate the effects of varying cation valency and
concentration on the rheology of entangled lambda DNA solutions. We show that
monovalent cations moderately increase the viscoelasticty of the solutions
mainly by stabilising linear condensation of lambda DNA ``monomers'' via
hybridisation of their sticky ends. On the contrary, divalent cations have a
far more complex and dramatic effect on the rheology of the solution and we
observe evidence of inter-molecular DNA-DNA bridging by Mg2+. We argue that
these results may be interesting in the context of dense solutions of single
and double stranded DNA, e.g. in vivo or in biotechnology applications such as
DNA origami and DNA hydrogels.Comment: 8 pages, 5 figure
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