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Arvind Murugan

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Published work

13 published item(s)

preprint2026arXiv

Conditioning as a route to stereotyped behavior in growing populations

Biological systems perform complex multi-step processes in a reproducible way despite underlying stochasticity. The standard explanation is micromanagement by molecular machinery that recognizes and corrects specific errors. Here we study conditioning, a qualitatively different strategy in which attempts failing a coarse criterion are destroyed and do not leave a physical record. The surviving, i.e., conditioned, ensemble is narrower and therefore more ordered. We model conditioning through stochastic resets in a ''socks-before-shoes'' model of a growing population, where $n$ actions must be completed in any order to replicate and any replication attempt not finished by a threshold time is discarded. We find that resets impose hierarchical temporal ordering of the $n$ actions without microscopic control over which action happens when. When disorder carries a sufficient time penalty, this ordering is free: the fastest-growing population is automatically the most ordered, with no direct selection for order required. Save points, at which verified progress is preserved across resets, allow conditioning to scale to complex multi-step processes. Conditioning provides a minimal route to reliable behavior, requiring only a clock rather than molecular machinery that recognizes specific errors. For the right class of processes, it pays for itself.

preprint2024arXiv

Dynamic coexistence driven by physiological transitions in microbial communities

Microbial ecosystems are commonly modeled by fixed interactions between species in steady exponential growth states. However, microbes often modify their environments so strongly that they are forced out of the exponential state into stressed or non-growing states. Such dynamics are typical of ecological succession in nature and serial-dilution cycles in the laboratory. Here, we introduce a phenomenological model, the Community State model, to gain insight into the dynamic coexistence of microbes due to changes in their physiological states. Our model bypasses specific interactions (e.g., nutrient starvation, stress, aggregation) that lead to different combinations of physiological states, referred to collectively as "community states", and modeled by specifying the growth preference of each species along a global ecological coordinate, taken here to be the total community biomass density. We identify three key features of such dynamical communities that contrast starkly with steady-state communities: increased tolerance of community diversity to fast growth rates of species dominating different community states, enhanced community stability through staggered dominance of different species in different community states, and increased requirement on growth dominance for the inclusion of late-growing species. These features, derived explicitly for simplified models, are proposed here to be principles aiding the understanding of complex dynamical communities. Our model shifts the focus of ecosystem dynamics from bottom-up studies based on idealized inter-species interaction to top-down studies based on accessible macroscopic observables such as growth rates and total biomass density, enabling quantitative examination of community-wide characteristics.

preprint2022arXiv

Non-Convex Optimization by Hamiltonian Alternation

A major obstacle to non-convex optimization is the problem of getting stuck in local minima. We introduce a novel metaheuristic to handle this issue, creating an alternate Hamiltonian that shares minima with the original Hamiltonian only within a chosen energy range. We find that repeatedly minimizing each Hamiltonian in sequence allows an algorithm to escape local minima. This technique is particularly straightforward when the ground state energy is known, and one obtains an improvement even without this knowledge. We demonstrate this technique by using it to find the ground state for instances of a Sherrington-Kirkpatrick spin glass.

preprint2020arXiv

Proofreading through spatial gradients

Key enzymatic processes in biology use the nonequilibrium error correction mechanism called kinetic proofreading to enhance their specificity. Kinetic proofreading typically requires several dedicated structural features in the enzyme, such as a nucleotide hydrolysis site and multiple enzyme-substrate conformations that delay product formation. Such requirements limit the applicability and the adaptability of traditional proofreading schemes. Here, we explore an alternative conceptual mechanism of error correction that achieves delays between substrate binding and subsequent product formation by having these events occur at distinct physical locations. The time taken by the enzyme-substrate complex to diffuse from one location to another is leveraged to discard wrong substrates. This mechanism does not require dedicated structural elements on the enzyme, making it easier to overlook in experiments but also making proofreading tunable on the fly. We discuss how tuning the length scales of enzyme or substrate concentration gradients changes the fidelity, speed and energy dissipation, and quantify the performance limitations imposed by realistic diffusion and reaction rates in the cell. Our work broadens the applicability of kinetic proofreading, and sets the stage for the study of spatial gradients as a possible route to specificity.

preprint2019arXiv

Learned multi-stability in mechanical networks

We contrast the distinct frameworks of materials design and physical learning in creating elastic networks with desired stable states. In design, the desired states are specified in advance and material parameters can be optimized on a computer with this knowledge. In learning, the material physically experiences the desired stable states in sequence, changing the material so as to stabilize each additional state. We show that while designed states are stable in networks of linear Hookean springs, sequential learning requires specific non-linear elasticity. We find that such non-linearity stabilizes states in which strain is zero in some springs and large in others, thus playing the role of Bayesian priors used in sparse statistical regression. Our model shows how specific material properties allow continuous learning of new functions through deployment of the material itself.

preprint2019arXiv

Tuning environmental timescales to evolve and maintain generalists

Natural environments can present diverse challenges, but some genotypes remain fit across many environments. Such `generalists' can be hard to evolve, out-competed by specialists fitter in any particular environment. Here, inspired by the search for broadly-neutralising antibodies during B-cell affinity maturation, we demonstrate that environmental changes on an intermediate timescale can reliably evolve generalists, even when faster or slower environmental changes are unable to do so. We find that changing environments on timescales comparable to evolutionary transients in a population enhances the rate of evolving generalists from specialists, without enhancing the reverse process. The yield of generalists is further increased in more complex dynamic environments, such as a `chirp' of increasing frequency. Our work offers design principles for how non-equilibrium fitness `seascapes' can dynamically funnel populations to genotypes unobtainable in static environments.

preprint2016arXiv

Receptor arrays optimized for natural odor statistics

Natural odors typically consist of many molecules at different concentrations. It is unclear how the numerous odorant molecules and their possible mixtures are discriminated by relatively few olfactory receptors. Using an information-theoretic model, we show that a receptor array is optimal for this task if it achieves two possibly conflicting goals: (i) each receptor should respond to half of all odors and (ii) the response of different receptors should be uncorrelated when averaged over odors presented with natural statistics. We use these design principles to predict statistics of the affinities between receptors and odorant molecules for a broad class of odor statistics. We also show that optimal receptor arrays can be tuned to either resolve concentrations well or distinguish mixtures reliably. Finally, we use our results to predict properties of experimentally measured receptor arrays. Our work can thus be used to better understand natural olfaction and it also suggests ways to improve artificial sensor arrays.

preprint2016arXiv

Renormalization group flows in gauge-gravity duality

This is a copy of the 2009 Princeton University thesis which examined various aspects of gauge/gravity duality, including renormalization group flows, phase transitions of the holographic entanglement entropy, and instabilities associated with the breaking of supersymmetry. Chapter 5 contains new unpublished material on various instabilities of the weakly curved non-supersymmetric $AdS_4$ backgrounds of M-theory.

preprint2016arXiv

The Information Capacity of Specific Interactions

Specific interactions are a hallmark feature of self-assembly and signal-processing systems in both synthetic and biological settings. Specificity between components may arise from a wide variety of physical and chemical mechanisms in diverse contexts, from DNA hybridization to shape-sensitive depletion interactions. Despite this diversity, all systems that rely on interaction specificity operate under the constraint that increasing the number of distinct components inevitably increases off-target binding. Here we introduce `capacity', the maximal information encodable using specific interactions, to compare specificity across diverse experimental systems, and to compute how specificity changes with physical parameters. Using this framework, we find that `shape'-coding of interactions has higher capacity than chemical (`color') coding because the strength of off-target binding is strongly sublinear in binding site size for shapes while being linear for colors. We also find that different specificity mechanisms, such as shape and color, can be combined in a synergistic manner, giving a capacity greater than the sum of the parts.

preprint2015arXiv

Biological implications of dynamical phases in non-equilibrium networks

Biology achieves novel functions like error correction, ultra-sensitivity and accurate concentration measurement at the expense of free energy through Maxwell Demon-like mechanisms. The design principles and free energy trade-offs have been studied for a variety of such mechanisms. In this review, we emphasize a perspective based on dynamical phases that can explain commonalities shared by these mechanisms. Dynamical phases are defined by typical trajectories executed by non-equilibrium systems in the space of internal states. We find that coexistence of dynamical phases can have dramatic consequences for function vs free energy cost trade-offs. Dynamical phases can also provide an intuitive picture of the design principles behind such biological Maxwell Demons.

preprint2014arXiv

Discriminatory proofreading regimes in non-equilibrium systems

We use ideas from kinetic proofreading, an error-correcting mechanism in biology, to identify new kinetic regimes in non-equilibrium systems. These regimes are defined by the sensitivity of the occupancy of a state of the system to a change in its energy. In biological contexts, higher sensitivity corresponds to stronger discrimination between molecular substrates with different energetics competing in the same reaction. We study this discriminatory ability in systems with discrete states that are connected by a general network of transitions. We find multiple regimes of different discriminatory ability when the energy of a given state of the network is varied. Interestingly, the occupancy of the state can even increase with its energy, corresponding to an "anti-proofreading" regime. The number and properties of such discriminatory regimes are limited by the topology of the network. Finally, we find that discriminatory regimes can be changed without modifying any "hard-wired" structural aspects of the system but rather by simply changing external chemical potentials.

preprint2014arXiv

Multifarious Assembly Mixtures: Systems Allowing Retrieval of Diverse Stored Structures

Self-assembly materials are traditionally designed so that molecular or meso-scale components form a single kind of large structure. Here, we propose a scheme to create "multifarious assembly mixtures", which self-assemble many different large structures from a set of shared components. We show that the number of multifarious structures stored in the solution of components increases rapidly with the number of different types of components. Yet, each stored structure can be retrieved by tuning only a few parameters, the number of which is only weakly dependent on the size of the assembled structure. Implications for artificial and biological self-assembly are discussed.

preprint2006arXiv

On D3-brane Potentials in Compactifications with Fluxes and Wrapped D-branes

We study the potential governing D3-brane motion in a warped throat region of a string compactification with internal fluxes and wrapped D-branes. If the Kahler moduli of the compact space are stabilized by nonperturbative effects, a D3-brane experiences a force due to its interaction with D-branes wrapping certain four-cycles. We compute this interaction, as a correction to the warped four-cycle volume, using explicit throat backgrounds in supergravity. This amounts to a closed-string channel computation of the loop corrections to the nonperturbative superpotential that stabilizes the volume. We demonstrate for warped conical spaces that the superpotential correction is given by the embedding equation specifying the wrapped four-cycle, in agreement with the general form proposed by Ganor. Our approach automatically provides a solution to the problem of defining a holomorphic gauge coupling on wrapped D7-branes in a background with D3-branes. Finally, our results have applications to cosmological inflation models in which the inflaton is modeled by a D3-brane moving in a warped throat.