38,654 research outputs found
Optically-controlled platforms for transfection and single- and sub-cellular surgery
Improving the resolution of biological research to the single- or sub-cellular level is of critical importance in a wide variety of processes and disease conditions. Most obvious are those linked to aging and cancer, many of which are dependent upon stochastic processes where individual, unpredictable failures or mutations in individual cells can lead to serious downstream conditions across the whole organism. The traditional tools of biochemistry struggle to observe such processes: the vast majority are based upon ensemble approaches analysing the properties of bulk populations, which means that the detail about individual constituents is lost. What are required, then, are tools with the precision and resolution to probe and dissect cells at the single-micron scale: the scale of the individual organelles and structures that control their function. In this review, we highlight the use of highly-focused laser beams to create systems providing precise control and specificity at the single cell or even single micron level. The intense focal points generated can directly interact with cells and cell membranes, which in conjunction with related modalities such as optical trapping provide a broad platform for the development of single and sub-cellular surgery approaches. These highly tuneable tools have demonstrated delivery or removal of material from cells of interest, but can simultaneously excite fluorescent probes for imaging purposes or plasmonic structures for very local heating. We discuss both the history and recent applications of the field, highlighting the key findings and developments over the last 40 years of biophotonics researc
Stochastic Physics, Complex Systems and Biology
In complex systems, the interplay between nonlinear and stochastic dynamics,
e.g., J. Monod's necessity and chance, gives rise to an evolutionary process in
Darwinian sense, in terms of discrete jumps among attractors, with punctuated
equilibrium, spontaneous random "mutations" and "adaptations". On an
evlutionary time scale it produces sustainable diversity among individuals in a
homogeneous population rather than convergence as usually predicted by a
deterministic dynamics. The emergent discrete states in such a system, i.e.,
attractors, have natural robustness against both internal and external
perturbations. Phenotypic states of a biological cell, a mesoscopic nonlinear
stochastic open biochemical system, could be understood through such a
perspective.Comment: 10 page
Diffusion Controlled Reactions, Fluctuation Dominated Kinetics, and Living Cell Biochemistry
In recent years considerable portion of the computer science community has
focused its attention on understanding living cell biochemistry and efforts to
understand such complication reaction environment have spread over wide front,
ranging from systems biology approaches, through network analysis (motif
identification) towards developing language and simulators for low level
biochemical processes. Apart from simulation work, much of the efforts are
directed to using mean field equations (equivalent to the equations of
classical chemical kinetics) to address various problems (stability,
robustness, sensitivity analysis, etc.). Rarely is the use of mean field
equations questioned. This review will provide a brief overview of the
situations when mean field equations fail and should not be used. These
equations can be derived from the theory of diffusion controlled reactions, and
emerge when assumption of perfect mixing is used
Error-speed correlations in biopolymer synthesis
Synthesis of biopolymers such as DNA, RNA, and proteins are biophysical
processes aided by enzymes. Performance of these enzymes is usually
characterized in terms of their average error rate and speed. However, because
of thermal fluctuations in these single-molecule processes, both error and
speed are inherently stochastic quantities. In this paper, we study
fluctuations of error and speed in biopolymer synthesis and show that they are
in general correlated. This means that, under equal conditions, polymers that
are synthesized faster due to a fluctuation tend to have either better or worse
errors than the average. The error-correction mechanism implemented by the
enzyme determines which of the two cases holds. For example, discrimination in
the forward reaction rates tends to grant smaller errors to polymers with
faster synthesis. The opposite occurs for discrimination in monomer rejection
rates. Our results provide an experimentally feasible way to identify
error-correction mechanisms by measuring the error-speed correlations.Comment: PDF file consist of the main text (pages 1 to 5) and the
supplementary material (pages 6 to 12). Overall, 7 figures split between main
text and S
Mesoscopic Biochemical Basis of Isogenetic Inheritance and Canalization: Stochasticity, Nonlinearity, and Emergent Landscape
Biochemical reaction systems in mesoscopic volume, under sustained
environmental chemical gradient(s), can have multiple stochastic attractors.
Two distinct mechanisms are known for their origins: () Stochastic
single-molecule events, such as gene expression, with slow gene on-off
dynamics; and () nonlinear networks with feedbacks. These two mechanisms
yield different volume dependence for the sojourn time of an attractor. As in
the classic Arrhenius theory for temperature dependent transition rates, a
landscape perspective provides a natural framework for the system's behavior.
However, due to the nonequilibrium nature of the open chemical systems, the
landscape, and the attractors it represents, are all themselves {\em emergent
properties} of complex, mesoscopic dynamics. In terms of the landscape, we show
a generalization of Kramers' approach is possible to provide a rate theory. The
emergence of attractors is a form of self-organization in the mesoscopic
system; stochastic attractors in biochemical systems such as gene regulation
and cellular signaling are naturally inheritable via cell division.
Delbr\"{u}ck-Gillespie's mesoscopic reaction system theory, therefore, provides
a biochemical basis for spontaneous isogenetic switching and canalization.Comment: 24 pages, 6 figure
A Stochastic model for dynamics of FtsZ filaments and the formation of Z-ring
Understanding the mechanisms responsible for the formation and growth of FtsZ
polymers and their subsequent formation of the -ring is important for
gaining insight into the cell division in prokaryotic cells. In this work, we
present a minimal stochastic model that qualitatively reproduces {\it in vitro}
observations of polymerization, formation of dynamic contractile ring that is
stable for a long time and depolymerization shown by FtsZ polymer filaments. In
this stochastic model, we explore different mechanisms for ring breaking and
hydrolysis. In addition to hydrolysis, which is known to regulate the dynamics
of other tubulin polymers like microtubules, we find that the presence of the
ring allows for an additional mechanism for regulating the dynamics of FtsZ
polymers. Ring breaking dynamics in the presence of hydrolysis naturally induce
rescue and catastrophe events in this model irrespective of the mechanism of
hydrolysis.Comment: Replaced with published versio
Analysis of signalling pathways using the prism model checker
We describe a new modelling and analysis approach for signal
transduction networks in the presence of incomplete data. We illustrate
the approach with an example, the RKIP inhibited ERK pathway
[1]. Our models are based on high level descriptions of continuous time
Markov chains: reactions are modelled as synchronous processes and concentrations
are modelled by discrete, abstract quantities. The main advantage
of our approach is that using a (continuous time) stochastic logic
and the PRISM model checker, we can perform quantitative analysis of
queries such as if a concentration reaches a certain level, will it remain at
that level thereafter? We also perform standard simulations and compare
our results with a traditional ordinary differential equation model. An
interesting result is that for the example pathway, only a small number
of discrete data values is required to render the simulations practically
indistinguishable
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