arXiv subjects

Henry H. Mattingly

Publications and source records attributed to Henry H. Mattingly.

6 recordsLinked to original sources

arXiv2026

Measurement-limited learning of conformational heterogeneity in cryo-electron microscopy

Cryogenic electron microscopy images sample individual biomolecules from their conformational landscapes, offering a route to infer the distributions underlying molecular mechanisms. However, because images are indirect measurements, they limit which features of an underlying landscape are statistically identifiable. In ensemble reweighting, this problem appears as a choice of resolution: conformational space is discretized into representative structures whose population weights are inferred from images. Adding structures increases nominal resolution, but nearby conformations may generate overlapping image distributions and indistinguishable weights. Here, we develop an information-theoretic framework that selects representative conformations by maximizing mutual information between ensemble weights and images under a probabilistic forward model. Analytically, we show in a one-dimensional Gaussian model that measurement noise sets the optimal spacing. Applied to molecular conformations sampled from simulation, the framework constructs near-optimal ensembles that span heterogeneity while avoiding redundancy. Thus, the measurement process induces a maximally learnable coarse graining of conformation space.

physics.bio-ph↗

arXiv2025

Chemotaxing E. coli do not count single molecules

Organisms use specialized sensors to measure their environments, but the fundamental principles that determine their accuracy remain largely unknown. In Escherichia coli chemotaxis, we previously found that gradient-climbing speed is bounded by the amount of information that cells acquire from their environment, and that E. coli operate near this bound. However, it remains unclear what prevents them from acquiring more information. Past work argued that E. coli's chemosensing is limited by the physics of molecules stochastically arriving at cells' receptors, without direct evidence. Here, we show instead that E. coli are far from this physical limit. To show this, we develop a theoretical approach that uses information rates to quantify how accurately behaviorally-relevant signals can be estimated from available observations: molecule arrivals for the physical limit; chemotaxis signaling activity for E. coli. Measuring these information rates in single-cell experiments across multiple background concentrations, we find that E. coli encode two orders of magnitude less information than the physical limit. Thus, E. coli chemosensing is limited by internal noise in signal processing rather than the physics of molecule diffusion, motivating investigation of what specific physical and biological constraints shaped the evolution of this prototypical sensory system.

physics.bio-ph↗

arXiv2025

Ultrasensitivity without conformational spread: A mechanical origin for non-equilibrium cooperativity in the bacterial flagellar motor

Flagellar motors enable bacteria to navigate their environments by switching rotation direction in response to external cues with high sensitivity. Previous work suggested that ultrasensitivity of the flagellar motor originates from conformational spread, in which subunits of the switching complex are strongly coupled to their neighbors as in an equilibrium Ising model. However, dynamic single-motor measurements indicated that rotation switching is driven out of equilibrium, and the mechanism for this dissipative driving remains unknown. Here, based on recent cryo-EM structures, we propose that local mechanical torques on motor subunits can affect their conformation dynamics. This gives rise to a tug of war between stator-associated subunits, which produces cooperative, non-equilibrium switching responses without requiring nearest-neighbor interactions. Since subunits are effectively coupled at a distance, we call this mechanism ``Global Mechanical Coupling." Our model makes a qualitatively new prediction that the motor response cooperativity grows with the number of stators driving rotation. Re-analyzing published motor dose-response curves in varying load conditions, we find tentative experimental evidence for this prediction. Finally, we show that operating out of equilibrium enables motors to achieve high cooperativity with faster responses compared to equilibrium motors. Our results suggest a general role for mechanics in sensitive chemical regulation.

physics.bio-ph↗

arXiv2023

Bacterial diffusion in disordered media, by forgetting the media

We study bacterial diffusion in disordered porous media. Interactions with obstacles, at unknown locations, make this problem challenging. We approach it by abstracting the environment to cell states with memoryless transitions. With this, we derive an effective diffusivity that agrees well with simulations in explicit geometries. The diffusivity is non-monotonic, and we solve the optimal run length. We also find a rescaling that causes all of the theory and simulations to collapse. Our results indicate that a small set of microscopic features captures bacterial diffusion in disordered media.

cond-mat.soft↗

arXiv2021

E. coli chemotaxis is information-limited

Organisms must acquire and use environmental information to guide their behaviors. However, it is unclear whether and how information quantitatively limits behavioral performance. Here, we relate information to behavioral performance in Escherichia coli chemotaxis. First, we derive a theoretical limit for the maximum achievable gradient-climbing speed given a cell's information acquisition rate. Next, we measure cells' gradient-climbing speeds and the rate of information acquisition by the chemotaxis pathway. We find that E. coli make behavioral decisions with much less than the 1 bit required to determine whether they are swimming up-gradient. However, they use this information efficiently, performing near the theoretical limit. Thus, information can limit organisms' performance, and sensory-motor pathways may have evolved to efficiently use information from the environment.

physics.bio-ph↗

arXiv2018

Maximizing the information learned from finite data selects a simple model

We use the language of uninformative Bayesian prior choice to study the selection of appropriately simple effective models. We advocate for the prior which maximizes the mutual information between parameters and predictions, learning as much as possible from limited data. When many parameters are poorly constrained by the available data, we find that this prior puts weight only on boundaries of the parameter manifold. Thus it selects a lower-dimensional effective theory in a principled way, ignoring irrelevant parameter directions. In the limit where there is sufficient data to tightly constrain any number of parameters, this reduces to Jeffreys prior. But we argue that this limit is pathological when applied to the hyper-ribbon parameter manifolds generic in science, because it leads to dramatic dependence on effects invisible to experiment.

physics.data-an↗