arXiv subjects

Michael J. Shelley

Publications and source records attributed to Michael J. Shelley.

At least 19 recordsLinked to original sources

arXiv2026

Polarization of the Drosophila oocyte by active cortical exchange

Anterior-posterior polarization in the Drosophila oocyte requires posterior localization of oskar mRNA. oskar mRNA is produced in the anteriorly situated nurse cells, moved into the oocyte, and assembled into oskar-Staufen ribonucleoprotein particles (RNPs). These RNPs then move through the oocyte and interact with the cortex, where myosin-V binds them to the actin network and kinesin-1 removes them along cortically anchored microtubules. This cortical tug-of-war takes place against an anterior-to-posterior decrease in microtubule density. How the interplay between cytoplasmic transport and cortical binding and unbinding produces a stable posterior cap is unclear. Here, we combine quantitative microscopy, photoconversion experiments, experimental perturbations, and biophysical modeling to show that posterior localization emerges from position-dependent cortical exchange coupled to cytoplasmic diffusion. Our model, which accounts for the tendency of RNPs to demix, suggests that two key parameters that determine the observed localization pattern are the total amount of oskar and the ratio of cortical unbinding to binding rates (the exchange equilibrium constant). Given oskar volume fractions in wild-type, the measured exchange constant is such that oskar localizes to the posterior cortex without demixing. If the balance is broken, say by increasing unbinding rates, oskar irreversibly demixes into cytoplasmic droplets. This is consistent with observations from our experimental perturbations. Our results show how bulk diffusion and cortical exchange, in the face of oskar RNPs' self-attraction, convert a cytoskeletal asymmetry into robust developmental polarity.

physics.bio-ph↗

arXiv2026

Traveling Waves Enhance Transport during Cytoplasmic Streaming in Drosophila Oogenesis

Cytoplasmic streaming is believed crucial to large developing cells, such as oocytes, where flow provides a much faster route to transport and mixing of cellular components than molecular diffusion. Molecular motors carrying cargoes on cytoskeletal elements are known to drive streaming in a variety of biological systems and, in Drosophila oocytes, cell-spanning vortical flows are tied to kinesin motors moving on dense beds of microtubules. Recent theories and simulations suggest such streaming self-organizes through interacting microtubules, motors, and flow. Whether these theoretically derived flows are adequate to the tasks of transport and mixing has been unclear. Here we report on new observations of coherent waves traveling persistently through microtubule beds during streaming, and investigate their impact on fluid transport and mixing. Leveraging recent advances in simulating the complex fluid-structure problems of cellular environments, we probe a biophysical model set in an oocytal geometry. Our simulations identify previously unknown waving states that show concordance with our experimental observation and the capacity for functional transport and mixing.

physics.bio-ph↗

arXiv2026

Growing, Buckling, and Swirling: motility from polymerization

Locomotion in low-Reynolds-number environments is achieved through a remarkable diversity of strategies, from flagellar rotation and ciliary beating to large-scale body deformations. A distinct and biologically important class of propulsion arises when surface-anchored filaments grow and collectively reorient - as seen in the cellulose-extruding bacterium Acetobacter xylinum and in recent experiments on actin-propelled synthetic colloids inspired by the motility of Listeria monocytogenes - suggesting that polymerization itself is a generic route to self-propulsion. Developing a theoretical framework for this class of problems requires simultaneously resolving filament kinetics, their orientational dynamics, and fluid-structure interactions - all self-consistently coupled to the resulting locomotion. To address this, we formulate a continuum framework in which the active forces driving locomotion emerge self-consistently from filament nucleation, growth, catastrophe, and hydrodynamic interactions. We show analytically that polymerization-induced compressive forces drive a long-wavelength buckling instability, leading to spontaneous symmetry breaking of the filament carpet and large-scale flows. In coupling this framework to a force- and torque-free motile spheroidal particle, a wide variety of behaviors emerge - this includes spontaneous spinning, directed motility, and chiral swimming - whose selection is governed by the spatial patterning of polymerizing filaments. These results establish a general theoretical foundation for motility, driven by collective dynamics of polymerizing filaments and point towards new design principles for synthetic micron-scale swimmers.

cond-mat.soft↗

arXiv2026

Traveling waves in a continuum model of schooling swimmers

The complex formations exhibited by schooling fish have long been the object of fascination for biologists and physicists. However, the physical and sensory mechanisms leading to organized collective behavior remain elusive. On the physical side in particular, it is unknown how the flows generated by individual fish influence the collective patterns that emerge in large schools. To address this question, we here present a continuum theory for a school of swimmers in an inline formation. The swimmers are modeled as flapping wings that interact through temporally nonlocal hydrodynamic forces, as arise when one swimmer moves through the lingering vortex wakes shed by the others, leading to a system of time-delay-differential equations. Through coarse-graining, we derive a system of partial differential equations for the evolution of swimmer density and collective vorticity-induced hydrodynamic force. Linear stability analysis of the governing equations shows that there is a range of swimmer densities for which the uniform (constant-density) state is unstable to perturbations. Numerical simulations {in periodic domains} reveal families of stable traveling wave solutions, where a uniform school destabilizes into a collection of densely populated "sub-schools" separated by relatively sparse regions that move as a propagating wave. We find that distinct propagating waves may be stable for the same set of kinematic parameters. We also find that finite schools can evolve into packets of coarsening traveling waves whose overall spreading is described by a rarefaction fan moving upstream and a terminating downstream shock. Generally, our results show that temporally nonlocal hydrodynamic interactions can lead to rich collective behavior in schools of swimmers.

physics.flu-dyn↗

arXiv2026

Rare transitions between collective states in an active fluid via a weakly nonlinear reduction

We study a model for a dilute suspension of rod-like particles swimming at constant velocity in a Stokes flow. As the translational diffusivity of the particles decreases, a two-dimensional uniform concentration of randomly aligned particles undergoes either a codimension-2 pitchfork bifurcation or a codimension-4 Hopf bifurcation, depending on the particles' swimming speed. We use a weakly nonlinear expansion to reduce the system to a low-dimensional one for the amplitudes of the bifurcating eigenmodes. The originality of our calculations lies in incorporating spatio-temporal white noise forcing. The stochastic forcing terms in the amplitude equations are derived analytically from the noise acting on the original system. Past the onset of the bifurcations, the particles deterministically self-organize into steady or oscillating states of collective motion. For the Hopf bifurcation scenario, two stable periodic orbits are found to coexist, each corresponding to a distinct collective dynamics. The stochastic forcing induces rare transitions between them. Owing to the low dimensionality of amplitude equations, steady and dynamical statistics can be computed directly from the Fokker-Planck equation, or via the Adaptive Multilevel Splitting (AMS) rare-event algorithm. In particular, extremely long mean transition times and associated out-of-equilibrium paths between the periodic orbits are obtained. These paths can be understood in light of the invariant manifolds of the low-dimensional system, which brings insights into the mechanism behind the transitions. We also performed fully nonlinear stochastic simulations and used the AMS algorithm directly on the full system. The statistics are in good quantitative agreement with those computed on the reduced systems, the latter being obtained at a considerably lower numerical cost.

physics.flu-dyn↗

arXiv2026

Learning biophysical models of gene regulation with probability flow matching

Cellular differentiation is governed by gene regulatory networks, the high-dimensional stochastic biochemical systems that determine the transcriptional landscape and mediate cellular responses to signals and perturbations. Although single-cell RNA sequencing provides quantitative snapshots of the transcriptome, current methods for inferring gene-regulatory dynamics often lack mechanistic interpretability and fail to generalize to unseen conditions. Here we introduce Probability Flow Matching (PFM), a scalable framework for learning biophysically consistent stochastic processes directly from time-resolved single-cell measurements. Applying PFM to three hematopoiesis datasets, we show that models with similar interpolation accuracy can encode fundamentally different dynamics, with only biophysically consistent formulations accurately capturing mechanisms of lineage transitions, fate specification, and gene perturbation responses. We further demonstrate that PFM accommodates unbalanced populations, enabling simultaneous inference of cellular proliferation and death dynamics. Together, these results establish PFM as a flexible, scalable framework for integrating mechanistic modeling with single-cell omics.

q-bio.MN↗

arXiv2025

Condensation dynamics of sticky and anchored flexible biopolymers

Cells regulate gene expression in part by forming DNA-protein condensates in the nucleus. While existing theories describe the equilibrium size and stability of such condensates, their dynamics remain less understood. Here, we use coarse-grained 3D Brownian-dynamics simulations to study how long, end-anchored biopolymers condense over time due to transient crosslinking. By tracking how clusters nucleate, merge, and disappear, we identify two dominant dynamical pathways, ripening and merging, that govern the progression from an uncompacted chain to a single condensate. We show how microscopic kinetic parameters, protein density, and mechanical constraints shape these pathways. Using insights from the simulations, we construct a minimal mechanistic free-energy model that captures the observed scaling behavior. Together, these results clarify the dynamical determinants of DNA and chromatin reorganization on timescales relevant to gene regulation.

cond-mat.soft↗

arXiv2025

Active Hydrodynamic Theory of Euchromatin and Heterochromatin

The genome contains genetic information essential for cell's life. The genome's spatial organization inside the cell nucleus is critical for its proper function including gene regulation. The two major genomic compartments -- euchromatin and heterochromatin -- contain largely transcriptionally active and silenced genes, respectively, and exhibit distinct dynamics. In this work, we present a hydrodynamic framework that describes the large-scale behavior of euchromatin and heterochromatin, and accounts for the interplay of mechanical forces, active processes, and nuclear confinement. Our model shows contractile stresses from cross-linking proteins lead to the formation of heterochromatin droplets via mechanically driven phase separation. These droplets grow, coalesce, and in nuclear confinement, wet the boundary. Active processes, such as gene transcription in euchromatin, introduce non-equilibrium fluctuations that drive long-range, coherent motions of chromatin as well as the nucleoplasm, and thus alter the genome's spatial organization. These fluctuations also indirectly deform heterochromatin droplets, by continuously changing their shape. Taken together, our findings reveal how active forces, mechanical stresses and hydrodynamic flows contribute to the genome's organization at large scales and provide a physical framework for understanding chromatin organization and dynamics in live cells.

cond-mat.soft↗

arXiv2025

Collective multicellular patterns arising from cadherin-linked cytoskeletal domains

In multicellular systems, adhesion complexes, such as those composed of E-cadherin and associated catenins, mechanically couple neighboring cells by directly linking their actin-based cytoskeletal assemblies. However, the mechanics of how forces are transmitted across these adhesions remains largely unstudied. Here, we introduce a biophysical model that explicitly couples adhesion complex dynamics to intracellular mechanics across cell boundaries. A cadherin dimer plus associated catenins connecting two cells is represented as a spring whose ends experience drag with respect to the moving actin cytoskeleton. The cytoskeleton is modeled as a contractile gel driven by myosin activity in its bulk and forces from adhesion on its boundaries. Our model captures this bidirectional coupling via a coarse-grained continuum framework and reveals a range of observed cell- and tissue-scale behaviors. These include global cell polarization of the multicellular collective, other polarization patterns and oscillatory dynamics, spontaneously formed actin rings within cells, and supracellular stress chains. Many of these features arise from modeling the direct mechanical coupling between cytoskeleton and adhesion. This model can be extended to other adhesion-cytoskeleton feedback systems and used to advance our understanding of multicellular tissue dynamics, particularly during development.

physics.bio-ph↗

arXiv2025

Active Liquid Crystal Theory Explains the Collective Organization of Microtubules in Human Mitotic Spindles

How thousands of microtubules and molecular motors self-organize into spindles remains poorly understood. By combining static, nanometer-resolution, large-scale electron tomography reconstructions and dynamic, optical-resolution, polarized light microscopy, we test an active liquid crystal continuum model of mitotic spindles in human tissue culture cells. The predictions of this coarse-grained theory quantitatively agree with the experimentally measured spindle morphology and fluctuation spectra. These findings argue that local interactions and polymerization produce collective alignment, diffusive-like motion, and polar transport which govern the behaviors of the spindle's microtubule network, and provide a means to measure the spindle's material properties. This work demonstrates that a coarse-grained theory featuring measurable, physically-interpretable parameters can quantitatively describe the mechanical behavior and self-organization of human mitotic spindles.

physics.bio-ph↗

arXiv2025

Stability of co-annular active and passive confined fluids

The translation and shape deformations of a passive viscous Newtonian droplet immersed in an active nematic liquid crystal under circular confinement are analyzed using a linear stability analysis. We focus on the case of a sharply aligned active nematic in the limit of strong elastic relaxation in two dimensions. Using an active liquid crystal model, we employ the Lorentz reciprocal theorem for Stokes flow to study the growth of interfacial perturbations as a result of both active and elastic stresses. Instabilities are uncovered in both extensile and contractile systems, for which growth rates are calculated and presented in terms of the dimensionless ratios of active, elastic, and capillary stresses, as well as the viscosity ratio between the two fluids. We also extend our theory to analyze the inverse scenario, namely, the stability of an active nematic droplet surrounded by a passive viscous layer. Our results highlight the subtle interplay of capillary, active, elastic, and viscous stresses in governing droplet stability. The instabilities uncovered here may be relevant to a plethora of biological active systems, from the dynamics of passive droplets in bacterial suspensions to the organization of subcellular compartments inside the cell and cell nucleus.

cond-mat.soft↗

arXiv2025

The physical consequences of sperm gigantism

The male fruit fly produces ~1.8 mm long sperm, thousands of which can be stored until mating in a ~200 micron sac, the seminal vesicle. While the evolutionary pressures driving such extreme sperm (flagellar) lengths have long been investigated, the physical consequences of their gigantism are unstudied. Through high-resolution three-dimensional reconstructions of in vivo sperm morphologies and rapid live imaging, we discovered that stored sperm are organized into a dense and highly aligned state. The packed flagella exhibit system-wide collective 'material' flows, with persistent and slow-moving topological defects; individual sperm, despite their extraordinary lengths, propagate rapidly through the flagellar material, moving in either direction along material director lines. To understand how these collective behaviors arise from the constituents' nonequilibrium dynamics, we conceptualize the motion of individual sperm as topologically confined to a reptation-like tube formed by its neighbors. Therein, sperm propagate through observed amplitude-constrained and internally driven flagellar bending waves, pushing off counter-propagating neighbors. From this conception, we derive a continuum theory that produces an extensile material stress that can sustain an aligned flagellar material. Experimental perturbations and simulations of active elastic filaments verify our theoretical predictions. Our findings suggest that active stresses in the flagellar material maintain the sperm in an unentangled, hence functional state, in both sexes, and establish giant sperm in their native habitat as a novel and physiologically relevant active matter system.

cond-mat.soft↗

arXiv2025

Correlations, mean-field limits, and transition to the concentrated regime in motile particle suspensions

Suspensions of swimming particles exhibit complex collective behaviors driven by hydrodynamic interactions, showing persistent large-scale flows and long-range correlations. While heavily studied, it remains unclear how such structures depend on the system size and swimmer concentration. To address these issues, we simulate very large systems of suspended swimmers across a range of system sizes and volume fractions. For this we use high-performance simulation tools that build on slender body theory and implicit resolution of steric interactions. At low volume fractions and long times, the particle simulations reveal dynamic flow structures and correlation functions that scale with the system size. These results are consistent with a mean-field limit and agree well with a corresponding kinetic theory. At higher concentrations, the system departs from mean-field behavior. Flow structures become cellular, and correlation lengths scale with the particle size. Here, translational motion is suppressed, while rotational dynamics dominate. These findings highlight the limitations of dilute mean-field models and reveal new behaviors in dense active suspensions.

cond-mat.soft↗

arXiv2025

Flow interactions and forward flight dynamics of tandem flapping wings

We examine theoretically the flow interactions and forward flight dynamics of tandem or in-line flapping wings. Two wings are driven vertically with prescribed heaving-and-plunging motions, and the horizontal propulsion speeds and positions are dynamically selected through aero- or hydro-dynamic interactions. Our simulations employ an improved vortex sheet method to solve for the locomotion of the pair within the collective flow field, and we identify 'schooling states' in which the wings travel together with nearly constant separation. Multiple terminal configurations are achieved by varying the initial conditions, and the emergent separations are approximately integer multiples of the wavelength traced out by each wing. We explain the stability of these states by perturbing the follower and mapping out an effective potential for its position in the leader's wake. Each equilibrium position is stabilized since smaller separations are associated with in-phase follower-wake motions that constructively reinforce the flow but lead to decreased thrust on the follower; larger separations are associated with antagonistic follower-wake motions, increased thrust, and a weakened collective wake. The equilibria and their stability are also corroborated by a linearized theory for the motion of the leader, the wake it produces, and its effect on the follower. We also consider a weakly-flapping follower driven with lower heaving amplitude than the leader. We identify 'keep-up' conditions for which the wings may still 'school' together despite their dissimilar kinematics, with the 'freeloading' follower passively assuming a favorable position within the wake that permits it to travel significantly faster than it would in isolation.

physics.flu-dyn↗

arXiv2024

Spatio-Temporal Dynamics of Nucleo-Cytoplasmic Transport

Nucleocytoplasmic transport is essential for cellular function, presenting a canonical example of rapid molecular sorting inside cells. It consists of a coordinated interplay between import/export of molecules in/out the cell nucleus. Here, we investigate the role of spatio-temporal dynamics of the nucleocytoplasmic transport and its regulation. We develop a biophysical model that captures the main features of the nucleocytoplasmic transport, in particular, its regulation through the Ran cycle. Our model yields steady-state profiles for the molecular components of the Ran cycle, their relaxation times, as well as the nuclear-to-cytoplasmic molecule ratio. We show that these quantities are affected by their spatial dynamics and heterogeneity within the nucleus. Specifically, we find that the spatial nonuniformity of Ran Guanine Exchange Factor (RanGEF) - particularly its proximity to the nuclear envelope - increases the Ran content in the nucleus. We further show that RanGEF's accumulation near the nuclear envelope results from its intrinsic dynamics as a nuclear cargo, transported by the Ran cycle itself. Overall, our work highlights the critical role of molecular spatial dynamics in cellular processes, and proposes new avenues for theoretical and experimental inquiries into the nucleocytoplasmic transport.

physics.bio-ph↗

arXiv2024

Geometric Effects in Large Scale Intracellular Flows

This work probes the role of cell geometry in orienting self-organized fluid flows in the late stage Drosophila oocyte. Recent theoretical work has shown that a model, which relies only on hydrodynamic interactions of flexible, cortically anchored microtubules (MTs) and the mechanical loads from molecular motors moving upon them, is sufficient to generate observed flows. While the emergence of flows has been studied in spheres, oocytes change shape during streaming and it was unclear how robust these flows are to the geometry of the cell. Here we use biophysical theory and computational analysis to investigate the role of geometry and find that the axis of rotation is set by the shape of the domain and that the flow is robust to biologically relevant perturbations of the domain shape. Using live imaging and 3D flow reconstruction, we test the predictions of the theory/simulation, finding consistency between the model and live experiments, further demonstrating a geometric dependence on flow direction in late-stage Drosophila oocytes.

physics.bio-ph↗

arXiv2024

A first-principles geometric model for dynamics of motor-driven centrosomal asters

The centrosomal aster is a mobile cellular organelle that exerts and transmits forces necessary for nuclear migration and spindle positioning. Recent experimental and theoretical studies of nematode and human cells demonstrate that pulling forces on asters by cortical force generators are dominant during such processes. We present a comprehensive investigation of a first-principles model of aster dynamics, the S-model (S for stoichiometry), based solely on such forces. The model evolves the astral centrosome position, a probability field of cell-surface motor occupancy by centrosomal microtubules (under an assumption of stoichiometric binding), and free boundaries of unattached, growing microtubules. We show how cell shape affects the centering stability of the aster, and its transition to oscillations with increasing motor number. Seeking to understand observations in single-cell nematode embryos, we use accurate simulations to examine the nonlinear structures of the bifurcations, and demonstrate the importance of binding domain overlap to interpreting genetic perturbation experiments. We find a rich dynamical landscape, dependent upon cell shape, such as internal equatorial orbits of asters that can be seen as traveling wave solutions. Finally, we study the interactions of multiple asters and demonstrate an effective mutual repulsion due to their competition for cortical force generators. We find, amazingly, that asters can relax onto the vertices of platonic and non-platonic solids, closely mirroring the results of the classical Thomson problem for energy-minimizing configurations of electrons constrained to a sphere and interacting via repulsive Coulomb potentials. Our findings both explain experimental observations, providing insights into the mechanisms governing spindle positioning and cell division dynamics, and show the possibility of new nonlinear phenomena in cell biology.

physics.bio-ph↗

arXiv2024

Mechanics and morphology of proliferating cell collectives with self-inhibiting growth

We study the dynamics of proliferating cell collectives whose microscopic constituents' growth is inhibited by macroscopic growth-induced stress. Discrete particle simulations of a growing collective show the emergence of concentric-ring patterns in cell size whose spatio-temporal structure is closely tied to the individual cell's stress response. Motivated by these observations, we derive a multiscale continuum theory whose parameters map directly to the discrete model. Analytical solutions of this theory show the concentric patterns arise from anisotropically accumulated resistance to growth over many cell cycles. This work shows how purely mechanical processes can affect the internal patterning and morphology of cell collectives, and provides a concise theoretical framework for connecting the micro- to macroscopic dynamics of proliferating matter.

physics.bio-ph↗