Search

The endoplasmic reticulum (ER) is a network of sheet-like and tubular structures that spans much of a cell and contains molecules undergoing diffusive searches for targets, such as unfolded proteins searching for chaperones and recently-folded proteins searching for export sites. By applying a Brownian dynamics algorithm to simulate molecule diffusion, we describe how ER tube geometry influences whether a searcher will encounter a nearby target or instead diffuse away to a region near to a distinct target, as well as the timescale of successful searches. We find that targets are more likely to be found for longer and narrower tubes, and larger targets, and that search in the tube volume is more sensitive to the search geometry compared to search on the tube surface. Our results suggest ER proteins searching for low-density targets in the membrane and the lumen are very likely to encounter the nearest target before diffusing to the vicinity of another target. Our results have implications for the design of target search simulations and calculations and interpretation of molecular trajectories on the ER network, as well as other organelles with tubular geometry., Comment: 13 pages, 8 figures

The endoplasmic reticulum (ER), a cellular organelle that forms a cell-spanning network of tubes and sheets, is an important location of protein synthesis and folding. When the ER experiences sustained unfolded protein stress, IRE1 proteins embedded in the ER membrane activate and assemble into clusters as part of the unfolded protein response (UPR). We use kinetic Monte Carlo simulations to explore IRE1 clustering dynamics on the surface of ER tubes. While initially growing clusters are approximately round, once a cluster is sufficiently large a shorter interface length can be achieved by `wrapping' around the ER tube. A wrapped cluster can grow without further interface length increases. Relative to wide tubes, narrower tubes enable cluster wrapping at smaller cluster sizes. Our simulations show that wrapped clusters on narrower tubes grow more rapidly, evaporate more slowly, and require a lower protein concentration to grow compared to equal-area round clusters on wider tubes. These results suggest that cluster wrapping, facilitated by narrower tubes, could be an important factor in the growth and stability of IRE1 clusters and thus impact the persistence of the UPR, connecting geometry to signaling behavior. This work is consistent with recent experimental observations of IRE1 clusters wrapped around narrow tubes in the ER network., Comment: 14 pages, 10 figures

We study a synthetic system of motile Escherichia coli bacteria encapsulated inside giant lipid vesicles. Forces exerted by the bacteria on the inner side of the membrane are sufficient to extrude membrane tubes filled with one or several bacteria. We show that a physical coupling between the membrane tube and the flagella of the enclosed cells transforms the tube into an effective helical flagellum propelling the vesicle. We develop a simple theoretical model to estimate the propulsive force from the speed of the vesicles, and demonstrate the good efficiency of this coupling mechanism. Together, these results point to design principles for conferring motility to synthetic cells., Comment: 22 pages, 12 figures

Bacteriophages spreading through populations of bacteria offer relatively simple, tuneable systems for testing mathematical models of range expansion. However, such models typically assume a static state into which to expand, which is not generally valid for bacterial-bacteriophage populations, where both the host (bacteria) and the infectious agent (bacteriophage) have similar growth rates. Here, we build on the classical FKPP theory of expanding fronts to study an infectious bacteriophage front propagating into an exponentially growing population of bacteria, focusing on the situation where the hosts are also mobile, e.g., swimming bacteria. In this case, both the infectious agent and the infected host populations take on the form of self-similar travelling waves with a fixed wave speed, as in FKPP theory, but the infected host wave also grows exponentially. Depending on the population under consideration, wave speeds are either advanced or retarded compared to the non-growing case. We identify a novel speed selection mechanism in which the shape of the bacteriophage wave controls these various wave speeds. We propose experiments to test our predictions., Comment: Main text: 21 pages, 4 main text figures, 6 appendix figures

The addition of enough non-adsorbing polymer to an otherwise stable colloidal suspension gives rise to a variety of phase behavior and kinetic arrest due to the depletion attraction induced between the colloids by the polymers. We report a study of these phenomena in a two-dimensional layer of colloids. The three-dimensional phenomenology of crystal-fluid coexistence is reproduced, but gelation takes a novel form, in which the strands in the gel structure are locally crystalline. We compare our findings with a previous simulation and theory, and find substantial agreement.

Several organelles in eukaryotic cells, including mitochondria and the endoplasmic reticulum, form interconnected tubule networks extending throughout the cell. These tubular networks host many biochemical pathways that rely on proteins diffusively searching through the network to encounter binding partners or localized target regions. In this work we develop both exact analytical methods to compute mean first passage times and efficient kinetic Monte Carlo algorithms to simulate trajectories of particles diffusing in a tubular network. Our approach leverages exact propagator functions for the distribution of transition times between network nodes and allows large simulation time steps determined by the network structure. The methodology is applied to both synthetic planar networks and organelle network structures, demonstrating key general features such as the heterogeneity of search times in different network regions and the functional advantage of broadly distributing target sites throughout the network. The proposed algorithms pave the way for future exploration of the interrelationship between tubular network structure and biomolecular reaction kinetics.

Newly-translated glycoproteins in the endoplasmic reticulum (ER) often undergo cycles of chaperone binding and release in order to assist in folding. Quality control is required to distinguish between proteins that have completed native folding, those that have yet to fold, and those that have misfolded. Using quantitative modeling, we explore how the design of the quality-control pathway modulates its efficiency. Our results show that an energy-consuming cyclic quality-control process, similar to the observed physiological system, outperforms alternative designs. The kinetic parameters that optimize the performance of this system drastically change with protein production levels, while remaining relatively insensitive to the protein folding rate. Adjusting only the degradation rate, while fixing other parameters, allows the pathway to adapt across a range of protein production levels, aligning with in vivo measurements that implicate the release of degradation-associated enzymes as a rapid-response system for perturbations in protein homeostasis. The quantitative models developed here elucidate design principles for effective glycoprotein quality control in the ER, improving our mechanistic understanding of a system crucial to maintaining cellular health., Comment: 22 pages, 8 figures

Much of the science underpinning the global response to the COVID-19 pandemic lies in the soft matter domain. Coronaviruses are composite particles with a core of nucleic acids complexed to proteins surrounded by a protein-studded lipid bilayer shell. A dominant route for transmission is via air-borne aerosols and droplets. Viral interaction with polymeric body fluids, particularly mucus, and cell membranes control their infectivity, while their interaction with skin and artificial surfaces underpins cleaning and disinfection and the efficacy of masks and other personal protective equipment. The global response to COVID-19 has highlighted gaps in the soft matter knowledge base. We survey these gaps, especially as pertaining to the transmission of the disease, and suggest questions that can (and need to) be tackled, both in response to COVID-19 and to better prepare for future viral pandemics., Comment: 15 pages

Biomolecular machines are protein complexes that convert between different forms of free energy. They are utilized in nature to accomplish many cellular tasks. As isothermal nonequilibrium stochastic objects at low Reynolds number, they face a distinct set of challenges compared to more familiar human-engineered macroscopic machines. Here we review central questions in their performance as free energy transducers, outline theoretical and modeling approaches to understand these questions, identify both physical limits on their operational characteristics and design principles for improving performance, and discuss emerging areas of research., Comment: 90 pages, 17 figures. Accepted version, with figure attribution and copyright statements corrected. This article is in press in Chemical Reviews, available online at https://doi.org/10.1021/acs.chemrev.9b00254

We investigate diffusive search on planar networks, motivated by tubular organelle networks in cell biology that contain molecules searching for reaction partners and binding sites. Exact calculation of the diffusive mean first-passage time on a spatial network is used to characterize the typical search time as a function of network connectivity. We find that global structural properties --- the total edge length and number of loops --- are sufficient to largely determine network exploration times for a variety of both synthetic planar networks and organelle morphologies extracted from living cells. For synthetic networks on a lattice, we predict the search time dependence on these global structural parameters by connecting with percolation theory, providing a bridge from irregular real-world networks to a simpler physical model. The dependence of search time on global network structural properties suggests that network architecture can be designed for efficient search without controlling the precise arrangement of connections. Specifically, increasing the number of loops substantially decreases search times, pointing to a potential physical mechanism for regulating reaction rates within organelle network structures., Comment: 13 pages, 4 figures. Accepted for publication in Scientific Reports

Biomolecular machines transduce free energy from one form to another to fulfill many important roles inside cells, with dissipation required to achieve directed progress. We investigate how to break time-reversal symmetry at a given dissipation cost by using deterministic protocols to drive systems over sawtooth potentials, which have frequently been used to model molecular machines as ratchets. Time asymmetry increases for sawtooth potentials with higher barriers and for driving potentials of intermediate width. For systems driven over a sawtooth potential according to a protocol, we find that symmetric sawtooths maximize time asymmetry, while earlier work examining ratchet models of molecular machines required asymmetric sawtooth potentials to achieve directed behavior. This distinction arises because deterministically driven machines are externally provided with direction, while autonomous machines must generate directed behavior., Comment: 8 pages, 5 figures

We use moving light patterns to control the motion of {\it Escherichia coli} bacteria whose motility is photo-activated. Varying the pattern speed controls the magnitude and direction of the bacterial flux, and therefore the accumulation of cells in up- and down-stream reservoirs. We validate our results with two-dimensional simulations and a 1-dimensional analytic model, and use these to explore parameter space. We find that cell accumulation is controlled by a competition between directed flux and undirected, stochastic transport. We articulate design principles for using moving light patterns and light-activated micro-swimmers to achieve particular experimental goals.

We consider sedimentation of a rigid helical filament in a viscous fluid under gravity. In the Stokes limit, the drag forces and torques on the filament are approximated within the resistive-force theory. We develop an analytic approximation to the exact equations of motion that works well in the limit of a sufficiently large number of turns in the helix (larger than two, typically). For a wide range of initial conditions, our approximation predicts that the centre of the helix itself follows a helical path with the symmetry axis of the trajectory being parallel to the direction of gravity. The radius and the pitch of the trajectory scale as non-trivial powers of the number of turns in the original helix. For the initial conditions corresponding to an almost horizontal orientation of the helix, we predict trajectories that are either attracted towards the horizontal orientation, in which case the helix sediments in a straight line along the direction of gravity, or trajectories that form a helical-like path with many temporal frequencies involved. Our results provide new insight into the sedimentation of chiral objects and might be used to develop new techniques for their spatial separation., Comment: 25 pages, 10 figures; accepted for publication in Physical Review Fluids

Biomolecular motors use free energy to drive a variety of cellular tasks, including the transport of cargo, such as vesicles and organelles. We find that the widely-used `constant-force' approximation for the effect of cargo on motor dynamics leads to a much larger variance of motor step number compared to explicitly modeling diffusive cargo, suggesting the constant-force approximation may be misapplied in some cases. We also find that, with cargo, motor progress is significantly more precise than suggested by a recent result. For cargo with a low relative diffusivity, the dynamics of continuous cargo motion---rather than discrete motor steps---dominate, leading to a new, more permissive bound on the precision of motor progress which is independent of the number of stages per motor cycle., Comment: 9 pages, 10 figures. This is the version of the article before peer review or editing, as submitted by an author to Europhysics Letters. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.1209/0295-5075/126/40004

We demonstrate differential dynamic microscopy and particle tracking for the characterization of the spatiotemporal behavior of active Janus colloids in terms of the intermediate scattering function (ISF). We provide an analytical solution for the ISF of the paradigmatic active Brownian particle model and find striking agreement with experimental results from the smallest length scales, where translational diffusion and self-propulsion dominate, up to the largest ones, which probe effective diffusion due to rotational Brownian motion. At intermediate length scales, characteristic oscillations resolve the crossover between directed motion to orientational relaxation and allow us to discriminate active Brownian motion from other reorientation processes, e.g., run-and-tumble motion. A direct comparison to theoretical predictions reliably yields the rotational and translational diffusion coefficients of the particles, the mean and width of their speed distribution, and the temporal evolution of these parameters.

Biomolecular machines transduce between different forms of energy. These machines make directed progress and increase their speed by consuming free energy, typically in the form of nonequilibrium chemical concentrations. Machine dynamics are often modeled by transitions between a set of discrete metastable conformational states. In general, the free energy change associated with each transition can increase the forward rate constant, decrease the reverse rate constant, or both. In contrast to previous optimizations, we find that in general flux is neither maximized by devoting all free energy changes to increasing forward rate constants nor by solely decreasing reverse rate constants. Instead the optimal free energy splitting depends on the detailed dynamics. Extending our analysis to machines with vulnerable states (from which they can break down), in the strong driving corresponding to in vivo cellular conditions, processivity is maximized by reducing the occupation of the vulnerable state., Comment: 22 pages, 7 figures

Biomolecular machines consume free energy to break symmetry and make directed progress. Nonequilibrium ATP concentrations are the typical free energy source, with one cycle of a molecular machine consuming a certain number of ATP, providing a fixed free energy budget. Since evolution is expected to favor rapid-turnover machines that operate efficiently, we investigate how this free energy budget can be allocated to maximize flux. Unconstrained optimization eliminates intermediate metastable states, indicating that flux is enhanced in molecular machines with fewer states. When maintaining a set number of states, we show that---in contrast to previous findings---the flux-maximizing allocation of dissipation is not even. This result is consistent with the coexistence of both `irreversible' and reversible transitions in molecular machine models that successfully describe experimental data, which suggests that in evolved machines different transitions differ significantly in their dissipation., Comment: 12 pages, 7 figures

Living things avoid equilibrium using molecular machines. Such microscopic soft-matter objects encounter relatively large friction and fluctuations. We discuss design principles for effective molecular machine operation in this unfamiliar context., Comment: To be published in "Physics in Canada", vol. 73, issue 2 (2017)

Selective autophagy must not only select the correct type of organelle, but also must discriminate between individual organelles of the same kind so that some but not all of the organelles are removed. We propose that physical clustering of autophagy receptor proteins on the organelle surface can provide an appropriate all-or-none signal for organelle degradation. We explore this proposal using a computational model restricted to peroxisomes and the relatively well characterized pexophagy receptor proteins NBR1 and p62. We find that larger peroxisomes nucleate NBR1 clusters first and lose them last through competitive coarsening. This results in significant size-selectivity that favors large peroxisomes, and can explain the increased catalase signal that results from siRNA inhibition of p62. Excess ubiquitin, resulting from damaged organelles, suppresses size-selectivity but not cluster formation. Our proposed selectivity mechanism thus allows all damaged organelles to be degraded, while otherwise selecting only a portion of organelles for degradation., Comment: 25 pages, 4 figures

An ion-exchange-resin-based microfluidic pump is introduced that utilizes trace amounts of ions to generate fluid flows. We show experimentally that our pump operates in almost deionized water for periods exceeding 24h and induces fluid flows of um/s over hundreds of um. This flow displays a far-field, power-law decay which is characteristic of two-dimensional (2D) flow when the system is strongly confined and of three-dimensional (3D) flow when it is not. Using theory and numerical calculations we demonstrate that our observations are consistent with electroosmotic pumping driven by umol/L ion concentrations in the sample cell that serve as 'fuel' to the pump. Our study thus reveals that trace amounts of charge carriers can produce surprisingly strong fluid flows; an insight that should benefit the design of a new class of microfluidic pumps that operate at very low fuel concentrations., Comment: 15 pages, 10 figures, 1 table

Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development. From the lack of new fibril formation after birth, we further require that the concentration of diffusing precursors stays below the critical concentration for fibril nucleation. We find that the combination of the diffusive bound, which requires larger concentrations to ensure homogeneous fibril radii, and lack of nucleation, which requires lower concentrations, is only marginally consistent with fully-processed collagen using conservative bounds. More realistic bounds may leave no consistent concentrations. Therefore, we propose that unprocessed pC-collagen diffuses from the bundle periphery followed by local C-proteinase activity and subsequent collagen incorporation at each fibril. We suggest that C-proteinase is localized within bundles, at fibril surfaces, during radial fibrillar growth. The much greater critical concentration of pC-collagen, as compared to fully-processed collagen, then provides broad consistency between homogeneous fibril radii and the lack of fibril nucleation during fibril growth., Comment: 10 pages, 2 figures

At molecular scales, fluctuations play a significant role and prevent biomolecular processes from always proceeding in a preferred direction, raising the question of how limited amounts of free energy can be dissipated to obtain directed progress. We examine the system and process characteristics that efficiently break time-reversal symmetry at fixed energy loss; in particular for a simple model of a molecular machine, an intermediate energy barrier produces unusually high asymmetry for a given dissipation. We relate the symmetry-breaking factors found in this model to recent observations of biomolecular machines., Comment: 9 pages, 3 figures

Water is a polar solvent and hence supports the bulk dissociation of itself and its solutes into ions, and the re-association of these ions into neutral molecules in a dynamic equilibrium, e.g., ${\rm H_2O_2}\leftrightharpoons {\rm H^+~+~HO_2^-}$. Using continuum theory, we study the influence of these reactions on the self-propulsion of colloids driven by surface chemical reactions (chemical swimmers) in aqueous solution. The association-dissociation reactions are here shown to have a strong influence on the swimmers' behaviour, and must therefore be included in future modelling. In particular, such bulk reactions permit charged swimmers to propel electrophoretically even if all species involved in the surface reactions are neutral. The bulk reactions also significantly modify the predicted speed of chemical swimmers propelled by ionic currents, by up to an order of magnitude. For swimmers whose surface reactions produce both anions and cations (ionic self-diffusiophoresis), the bulk reactions produce an additional reactive screening length, analogous to the Debye length in electrostatics. This in turn leads to an inverse relationship between swimmer radius and swimming speed, which could provide an alternative explanation for recent experimental observations on Pt-polystyrene Janus swimmers [S. Ebbens et al., Phys. Rev. E 85, 020401 (2012)]. We also use our continuum theory to investigate the effect of the Debye screening length itself, going beyond the infinitely thin limit approximation used by previous analytical theories. We identify significant departures from this limiting behavior for micron-sized swimmers under typical experimental conditions, and find that the limiting behavior fails entirely for nanoscale swimmers., Comment: 25 pages, 12 figures

We present a lattice Boltzmann study of the hydrodynamics of a fully resolved squirmer, radius R, confined in a slab of fluid between two no-slip walls. We show that the coupling between hydrodynamics and short-range repulsive interactions between the swimmer and the surface can lead to hydrodynamic trapping of both pushers and pullers at the wall, and to hydrodynamic oscillations in the case of a pusher. We further show that a pusher moves significantly faster when close to a surface than in the bulk, whereas a puller undergoes a transition between fast motion and a dynamical standstill according to the range of the repulsive interaction. Our results critically require near-field hydrodynamics; they further suggest that it should be possible to control density and speed of squirmers at a surface by tuning the range of steric and electrostatic swimmer-wall interactions., Comment: 5 + 8 pages, 4 + 4 Figures

We study catalytic Janus swimmers and Escherichia coli bacteria swimming in a two-dimensional colloidal crystal. The Janus swimmers orbit individual colloids and hop between colloids stochastically, with a hopping rate that varies inversely with fuel (hydrogen peroxide) concentration. At high fuel concentration, these orbits are stable for 100s of revolutions, and the orbital speed oscillates periodically as a result of hydrodynamic, and possibly also phoretic, interactions between the swimmer and the six neighbouring colloids. Motile E.~coli bacteria behave very differently in the same colloidal crystal: their circular orbits on plain glass are rectified into long, straight runs, because the bacteria are unable to turn corners inside the crystal.

Mammalian tissues contain networks and ordered arrays of collagen fibrils originating from the periodic self-assembly of helical 300 nm long tropocollagen complexes. The fibril radius is typically between 25 to 250 nm, and tropocollagen at the surface appears to exhibit a characteristic twist-angle with respect to the fibril axis. Similar fibril radii and twist-angles at the surface are observed in vitro, suggesting that these features are controlled by a similar self-assembly process. In this work, we propose a physical mechanism of equilibrium radius control for collagen fibrils based on a radially varying double-twist alignment of tropocollagen within a collagen fibril. The free-energy of alignment is similar to that of liquid crystalline blue phases, and we employ an analytic Euler-Lagrange and numerical free energy minimization to determine the twist-angle between the molecular axis and the fibril axis along the radial direction. Competition between the different elastic energy components, together with a surface energy, determines the equilibrium radius and twist-angle at the fibril surface. A simplified model with a twist-angle that is linear with radius is a reasonable approximation in some parameter regimes, and explains a power-law dependence of radius and twist-angle at the surface as parameters are varied. Fibril radius and twist-angle at the surface corresponding to an equilibrium free-energy minimum are consistent with existing experimental measurements of collagen fibrils. Remarkably, in the experimental regime, all of our model parameters are important for controlling equilibrium structural parameters of collagen fibrils., Comment: Accepted for publication in Soft Matter, DOI: 10.1039/c4sm01359j

The twin-arginine translocation (Tat) system transports folded proteins of various sizes across both bacterial and plant thylakoid membranes. The membrane-associated TatA protein is an essential component of the Tat translocon, and a broad distribution of different sized TatA-clusters is observed in bacterial membranes. We assume that the size dynamics of TatA clusters are affected by substrate binding, unbinding, and translocation to associated TatBC clusters, where clusters with bound translocation substrates favour growth and those without associated substrates favour shrinkage. With a stochastic model of substrate binding and cluster dynamics, we numerically determine the TatA cluster size distribution. We include a proportion of targeted but non-translocatable (NT) substrates, with the simplifying hypothesis that the substrate translocatability does not directly affect cluster dynamical rate constants or substrate binding or unbinding rates. This amounts to a translocation model without specific quality control. Nevertheless, NT substrates will remain associated with TatA clusters until unbound and so will affect cluster sizes and translocation rates. We find that the number of larger TatA clusters depends on the NT fraction $f$. The translocation rate can be optimized by tuning the rate of spontaneous substrate unbinding, $\Gamma_U$. We present an analytically solvable three-state model of substrate translocation without cluster size dynamics that follows our computed translocation rates, and that is consistent with {\em in vitro} Tat-translocation data in the presence of NT substrates., Comment: 20 pages, Accepted for publication in Physical Biology - This is not a copy edited version of the manuscript

When deprived of fixed nitrogen (fN), certain filamentous cyanobacteria differentiate nitrogen-fixing heterocysts. There is a large and dynamic fraction of stored fN in cyanobacterial cells, but its role in directing heterocyst commitment has not been identified. We present an integrated computational model of fN transport, cellular growth, and heterocyst commitment for filamentous cyanobacteria. By including fN storage proportional to cell length, but without any explicit cell-cycle effect, we are able to recover a broad and late range of heterocyst commitment times and we observe a strong indirect cell-cycle effect. We propose that fN storage is an important component of heterocyst commitment and patterning in filamentous cyanobacteria. The model allows us to explore both initial and steady-state heterocyst patterns. The developmental model is hierarchical after initial commitment: our only source of stochasticity is observed growth rate variability. Explicit lateral inhibition allows us to examine $\Delta$patS, $\Delta$hetN, and $\Delta$patN phenotypes. We find that $\Delta$patS leads to adjacent heterocysts of the same generation, while $\Delta$hetN leads to adjacent heterocysts only of different generations. With a shortened inhibition range, heterocyst spacing distributions are similar to those in experimental $\Delta$patN systems. Step-down to non-zero external fixed nitrogen concentrations is also investigated., Comment: This is an author-created, un-copyedited version of an article accepted for publication in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher-authenticated version will be available online

Under conditions of limited fixed-nitrogen, some filamentous cyanobacteria develop a regular pattern of heterocyst cells that fix nitrogen for the remaining vegetative cells. We examine three different heterocyst placement strategies by quantitatively modelling filament growth while varying both external fixed-nitrogen and leakage from the filament. We find that there is an optimum heterocyst frequency which maximizes the growth rate of the filament; the optimum frequency decreases as the external fixed-nitrogen concentration increases but increases as the leakage increases. In the presence of leakage, filaments implementing a local heterocyst placement strategy grow significantly faster than filaments implementing random heterocyst placement strategies. With no extracellular fixed-nitrogen, consistent with recent experimental studies of Anabaena sp. PCC 7120, the modelled heterocyst spacing distribution using our local heterocyst placement strategy is qualitatively similar to experimentally observed patterns. As external fixed-nitrogen is increased, the spacing distribution for our local placement strategy retains the same shape while the average spacing between heterocysts continuously increases., Comment: This is an author-created, un-copyedited version of an article accepted for publication in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher-authenticated version will be available online

Filamentous cyanobacteria growing in media with insufficient fixed nitrogen differentiate some cells into heterocysts, which fix nitrogen for the remaining vegetative cells. Transport studies have shown both periplasmic and cytoplasmic connections between cells that could transport fixed-nitrogen along the filament. Two experiments have imaged fixed-nitrogen distributions along filaments. In 1974,Wolk et al found a peaked concentration of fixed-nitrogen at heterocysts using autoradiographic techniques. In contrast, in 2007, Popa et al used nanoSIMS to show large dips at the location of heterocysts, with a variable but approximately level distribution between them. With an integrated model of fixed-nitrogen transport and cell growth, we recover the results of both Wolk et al and of Popa et al using the same model parameters. To do this, we account for immobile incorporated fixed-nitrogen and for the differing durations of labeled nitrogen fixation that occurred in the two experiments. The variations seen by Popa et al are consistent with the effects of cell-by-cell variations of growth rates, and mask diffusive gradients. We are unable to rule out a significant amount of periplasmic fN transport., Comment: This is an author-created, un-copyedited version of an article accepted for publication in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher-authenticated version will be available online