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Sean Fancher

Publications and source records attributed to Sean Fancher.

14 recordsLinked to original sources

Design principles for energy dissipation in viscoelastic network metamaterials

Mechanical energy dissipation in networked materials is relevant for applications from vibration isolation to impact protection, yet identifying optimal dissipative architectures in large disordered truss networks is computationally prohibitive with conventional finite element methods. We develop an efficient graph Laplacian-based spectral framework for viscoelastic truss networks, in which the full continuum dynamics of each rod are retained exactly and the problem size scales with the number of joints rather than element-level discretization points. Using this framework, we investigate how redistributing cross-sectional areas within a network (without changing material composition) controls energy dissipation. We find that random redistribution typically reduces dissipation relative to a uniform baseline, while gradient-based optimization yields nontrivial architectures whose form is governed by the intrinsic attenuation length of the base material. Focusing on driving frequencies near a global resonant mode of the network, we show that the optimal mass distribution decays from the source (driven joint) with the attenuation length scale, and at small attenuation lengths the optimal architecture is independent of the boundary conditions. These results motivate future studies of dissipation length scale based design principles on more complex disordered architectures and provide an efficient computational framework for exploring such structures at scale.

cond-mat.soft

Topological building blocks of nonequilibrium response

Nonequilibrium systems can exploit energy to amplify their sensitivity to external stimuli, allowing them to be harnessed for a variety of functions in both engineered devices and living organisms. An assortment of theoretical results capture different facets of this nonequilibrium amplification, including fluctuation-response relations as well as bounds and constraints that limit the potential behavior. Here, we take a broader perspective, aiming for a systematic characterization of the full range of possible response behaviors. For a wide class of nonequilibrium dynamics, we identify a collection of optimally sensitive models whose behavior is determined by the topology of the state space. We further conjecture that every response can be written as a convex combination of these optimal models, thereby structuring the entire space of responses. We use this geometric perspective to put sensitivity limits on nonmonotonic biochemical input-output functions, and identify all optimal kinetic schemes for the unordered binding of molecules among three sites.

cond-mat.stat-mech

Effects of cell-cell communication on bacterial chemotaxis

Bacteria track chemical gradients using a biased random walk, a process called chemotaxis. Experiments suggest that bacteria also communicate during this process. Using a mathematical model, we find that sufficiently strong communication succeeds in keeping a population of bacteria together but slows down chemotaxis. However, if the secretion of the communication molecule is coupled to the detection of the external chemoattractant, chemotaxis can be faster than without communication. Intriguingly, in this regime we predict that, even though blocking the communication receptors should slow down chemotaxis, partially blocking or underexpressing them should speed it up. Our work provides physical insights on how communication and chemotaxis are connected and may help explain why chemotaxing bacteria communicate.

physics.bio-ph

An efficient spectral method for the dynamic behavior of truss structures

Truss structures at macro-scale are common in a number of engineering applications and are now being increasingly used at the micro-scale to construct metamaterials. In analyzing the properties of a given truss structure, it is often necessary to understand how stress waves propagate through the system and/or its dynamic modes under time dependent loading so as to allow for maximally efficient use of space and material. This can be a computationally challenging task for particularly large or complex structures, with current methods requiring fine spatial discretization or evaluations of sizable matrices. Here we present a spectral method to compute the dynamics of trusses inspired by results from fluid flow networks. Our model accounts for the full dynamics of linearly elastic truss elements via a network Laplacian; a matrix object which couples the motions of the structure joints. We show that this method is equivalent to the continuum limit of linear finite element methods as well as capable of reproducing natural frequencies and modes determined by more complex and computationally costlier methods.

math.NA

Pulsatile Driving Stabilizes Loops in Elastic Flow Networks

Existing models of adaptation in biological flow networks consider their constituent vessels (e.g. veins and arteries) to be rigid, thus predicting a non physiological response when the drive (e.g. the heart) is dynamic. Here we show that incorporating pulsatile driving and properties such as fluid inertia and vessel compliance into a general adaptation framework fundamentally changes the expected structure at steady state of a minimal one-loop network. In particular, pulsatility is observed to give rise to resonances which can stabilize loops for a much broader class of metabolic cost functions than predicted by existing theories. Our work points to the need for a more realistic treatment of adaptation in biological flow networks, especially those driven by a pulsatile source, and provides insights into pathologies that emerge when such pulsatility is disrupted in human beings.

nlin.AO

Mechanical response in elastic fluid flow networks

The dynamics of flow within a material transport network is dependent upon the dynamics of its power source. Responding to a change of these dynamics is critical for the fitness of living flow networks, e.g. the animal vasculature, which are subject to frequent and sudden shifts when the pump (the heart) transitions between different steady states. The combination of flow resistance, fluid inertia, and elasticity of the vessel walls causes the flow and pressure of the fluid throughout the network to respond to these transitions and adapt to the new power source operating profiles over a nonzero time scale. We find that this response time can exist in one of two possible regimes; one dominated by the decay rate of travelling wavefronts and independent of system size, and one dominated by the diffusive nature of the fluid mechanical energy over large length scales. These regimes are shown to exist for both single vessels and hierarchically structured networks with systems smaller than a critical size in the former and larger systems in the later. Applying biologically relevant parameters to the model suggests that animal vascular networks may have evolved to occupy a state within the minimal response time regime but close to this critical system size.

physics.flu-dyn

Tradeoffs between energy efficiency and mechanical response in fluid flow networks

Transport networks are typically optimized, either by evolutionary pressures in biological systems or by human design in engineered structures. In the case of systems such as the animal vasculature, the transport of fluids is hindered by the inherent viscous resistance to flow while being kept in a dynamic state by the pulsatile nature of the heart and elastic properties of the vessel walls. While this imparted pulsatility necessarily increases the dissipation of energy caused by the resistance, the vessel elasticity helps to reduce overall dissipation by attenuating the amplitude of the pulsatile components of the flow. However, we find that this reduction in energy loss comes at the price of increasing the time required to respond to changes in the flow boundary conditions for vessels longer than a critical size. In this regime, dissipation and response time are found to follow a simple power law scaling relation both in single vessels as well as hierarchically structured networks. We validate the model in human vasculature and apply biologically relevant parameters to show that response time has to be considered alongside dissipation as an important fitness cost function in the evolutionary optimization of animal vascular networks.

physics.bio-ph

Precision of flow sensing by self-communicating cells

Metastatic cancer cells detect the direction of lymphatic flow by self-communication: they secrete and detect a chemical which, due to the flow, returns to the cell surface anisotropically. The secretion rate is low, meaning detection noise may play an important role, but the sensory precision of this mechanism has not been explored. Here we derive the precision of flow sensing for two ubiquitous detection methods: absorption vs.\ reversible binding to surface receptors. We find that binding is more precise due to the fact that absorption distorts the signal that the cell aims to detect. Comparing to experiments, our results suggest that the cancer cells operate remarkably close to the physical detection limit. Our prediction that cells should bind the chemical reversibly, not absorb it, is supported by endocytosis data for this ligand-receptor pair.

physics.bio-ph

Temporal precision of molecular events with regulation and feedback

Cellular behaviors such as migration, division, and differentiation rely on precise timing, and yet the molecular events that govern these behaviors are highly stochastic. We investigate regulatory strategies that decrease the timing noise of molecular events. Autoregulatory feedback increases noise. Yet, we find that in the presence of regulation by a second species, autoregulatory feedback decreases noise. To explain this finding, we develop a method to calculate the optimal regulation function that minimizes the timing noise. The method reveals that the combination of feedback and regulation minimizes noise by maximizing the number of molecular events that must happen in sequence before a threshold is crossed. We compute the optimal timing precision for all two-node networks with regulation and feedback, derive a generic lower bound on timing noise, and discuss our results in the context of neuroblast migration during Caenorhabditis elegans development.

physics.bio-ph

Diffusion vs. direct transport in the precision of morphogen readout

Morphogen profiles allow cells to determine their position within a developing organism, but the mechanisms behind the formation of these profiles are still not well agreed upon. Here we derive fundamental limits to the precision of morphogen concentration sensing for two canonical models: the diffusion of morphogen through extracellular space and the direct transport of morphogen from source cell to target cell, e.g. via cytonemes. We find that direct transport establishes a morphogen profile without adding extrinsic noise. Despite this advantage, we find that for sufficiently large values of population size and profile length, the diffusion mechanism is many times more precise due to a higher refresh rate of morphogen molecules. Our predictions are supported by data from a wide variety of morphogens in developing organisms.

physics.bio-ph

Emergent versus Individual-based Multicellular Chemotaxis

Multicellular chemotaxis can occur via individually chemotaxing cells that are mechanically coupled. Alternatively, it can emerge collectively, from cells chemotaxing differently in a group than they would individually. Here we consider collective movement that emerges from cells on the exterior of the collective responding to chemotactic signals, whereas bulk cells remain uninvolved in sensing and directing the collective. We find that the precision of this type of emergent chemotaxis is higher than that of individual-based chemotaxis for one-dimensional cell chains and two-dimensional cell sheets, but not three-dimensional cell clusters. We describe the physical origins of these results, discuss their biological implications, and show how they can be tested using common experimental measures such as the chemotactic index.

physics.bio-ph

Fundamental limits to collective concentration sensing in cell populations

The precision of concentration sensing is improved when cells communicate. Here we derive the physical limits to concentration sensing for cells that communicate over short distances by directly exchanging small molecules (juxtacrine signaling), or over longer distances by secreting and sensing a diffusive messenger molecule (autocrine signaling). In the latter case, we find that the optimal cell spacing can be large, due to a tradeoff between maintaining communication strength and reducing signal cross-correlations. This leads to the surprising result that autocrine signaling allows more precise sensing than juxtacrine signaling for sufficiently large populations. We compare our results to data from a wide variety of communicating cell types.

physics.bio-ph

Role of spatial averaging in multicellular gradient sensing

Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from analyses of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation--global inhibition (LEGI). The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation--global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations.

q-bio.MN

Stochastic modeling of gene expression, protein modification, and polymerization

Many fundamental cellular processes involve small numbers of molecules. When numbers are small, fluctuations dominate, and stochastic models, which account for these fluctuations, are required. In this chapter, we describe minimal stochastic models of three fundamental cellular processes: gene expression, protein modification, and polymerization. We introduce key analytic tools for solving each model, including the generating function, eigenfunction expansion, and operator methods, and we discuss how these tools are extended to more complicated models. These analytic tools provide an elegant, efficient, and often insightful alternative to stochastic simulation.

q-bio.MN