It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy.

Construction of a genetic toggle switch in Escherichia coli

Cell motility in viscous fluids is ubiquitous and affects many biological processes, including reproduction, infection and the marine life ecosystem. Here we review the biophysical and mechanical principles of locomotion at the small scales relevant to cell swimming, tens of micrometers and below. At this scale, inertia is unimportant and the Reynolds number is small. Our emphasis is on the simple physical picture and fundamental flow physics phenomena in this regime. We first give a brief overview of the mechanisms for swimming motility, and of the basic properties of flows at low Reynolds number, paying special attention to aspects most relevant for swimming such as resistance matrices for solid bodies, flow singularities and kinematic requirements for net translation. Then we review classical theoretical work on cell motility, in particular early calculations of swimming kinematics with prescribed stroke and the application of resistive force theory and slender-body theory to flagellar locomotion. After examining the physical means by which flagella are actuated, we outline areas of active research, including hydrodynamic interactions, biological locomotion in complex fluids, the design of small-scale artificial swimmers and the optimization of locomotion strategies. (Some figures in this article are in colour only in the electronic version) This article was invited by Christoph Schmidt.

/pdf/the-hydrodynamics-of-swimming-microorganisms-bonwl3c7w2.pdf

The hydrodynamics of swimming microorganisms

Surface-tension-driven flows and, in particular, their tendency to decay spontaneously into drops have long fascinated naturalists, the earliest systematic experiments dating back to the beginning of the 19th century. Linear stability theory governs the onset of breakup and was developed by Rayleigh, Plateau, and Maxwell. However, only recently has attention turned to the nonlinear behavior in the vicinity of the singular point where a drop separates. The increased attention is due to a number of recent and increasingly refined experiments, as well as to a host of technological applications, ranging from printing to mixing and fiber spinning. The description of drop separation becomes possible because jet motion turns out to be effectively governed by one-dimensional equations, which still contain most of the richness of the original dynamics. In addition, an attraction for physicists lies in the fact that the separation singularity is governed by universal scaling laws, which constitute an asymptotic solution of the Navier-Stokes equation before and after breakup. The Navier-Stokes equation is thus continued uniquely through the singularity. At high viscosities, a series of noise-driven instabilities has been observed, which are a nested superposition of singularities of the same universal form. At low viscosities, there is rich scaling behavior in addition to aesthetically pleasing breakup patterns driven by capillary waves. The author reviews the theoretical development of this field alongside recent experimental work, and outlines unsolved problems.

/pdf/nonlinear-dynamics-and-breakup-of-free-surface-flows-2oabav2z0g.pdf

Nonlinear dynamics and breakup of free-surface flows

Jets, ie collimated streams of matter, occur from the microscale up to the large-scale structure of the universe Our focus will be mostly on surface tension effects, which result from the cohesive properties of liquids Paradoxically, cohesive forces promote the breakup of jets, widely encountered in nature, technology and basic science, for example in nuclear fission, DNA sampling, medical diagnostics, sprays, agricultural irrigation and jet engine technology Liquid jets thus serve as a paradigm for free-surface motion, hydrodynamic instability and singularity formation leading to drop breakup In addition to their practical usefulness, jets are an ideal probe for liquid properties, such as surface tension, viscosity or non-Newtonian rheology They also arise from the last but one topology change of liquid masses bursting into sprays Jet dynamics are sensitive to the turbulent or thermal excitation of the fluid, as well as to the surrounding gas or fluid medium The aim of this review is to provide a unified description of the fundamental and the technological aspects of these subjects

Physics of liquid jets

Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecule...

/pdf/diffusion-in-brain-extracellular-space-4beypnugcc.pdf

Diffusion in brain extracellular space.

Introduction to mathematical biology

Slow flow of a viscous incompressible fluid past a slender body of circular crosssection is treated by the method of matched asymptotic expansions. The main result is an integral equation for the force per unit length exerted on the body by the fluid. The novelty is that the body is permitted to twist and dilate in addition to undergoing the translating, bending and stretching, which have been considered by others. The method of derivation is relatively simple, and the resulting integral equation does not involve the limiting processes which occur in the previous work.

/pdf/slender-body-theory-for-slow-viscous-flow-471s4j0bfq.pdf

Slender-body theory for slow viscous flow

The instability of a circular cylindrical jet of liquid in air is studied on the assumption that the wavenumber k of the disturbance is complex while its frequency σ is real. This implies that the disturbance grows with distance along the jet, but that it does not grow with time. The occurence of such disturbances is called spatial instability, in contrast to the temporal instability studied by Rayleigh and others, in which k is real and σ is complex. It is found that there are infinitely many unstable modes for the axially symmetric case and also for each of the asymmetric cases. In the case of high velocity jets, one of these modes for the symmetric case corresponds to the mode Rayleigh found. However, it is not the most rapidly growing mode. Both analytical and numerical solutions of the dispersion equation are given for k as a function of σ and of the dimensionless jet velocity.

Spatial instability of a jet

An elastic tube of circular cross section or an elastic ring can buckle if p, the outside pressure minus the inside pressure, exceeds the buckling pressure $p_{b2} $. As p increases above $p_{b2} $...

Post Buckling Behavior of Elastic Tubes and Rings with Opposite Sides in Contact

http://www.damtp.cam.ac.uk/user/gold/pdfs/KellerRubinow_swim.pdf

S. I. Rubinow

Papers

Introduction to mathematical biology

Slender-body theory for slow viscous flow

Spatial instability of a jet

Post Buckling Behavior of Elastic Tubes and Rings with Opposite Sides in Contact

Swimming of flagellated microorganisms.