arXiv subjects

Elena F. Koslover

Publications and source records attributed to Elena F. Koslover.

8 recordsLinked to original sources

arXiv2026

Diffusive Spreading Across Dynamic Mitochondrial Network Architectures

In eukaryotic cells, mitochondria form networks that range from highly fused interconnected structures to fragmented populations of individual organelles that undergo transient interactions. These structures can be described as temporal networks of physical units, whose dynamic topology is determined by fusion, fission, and motion of the mitochondria through intracellular space. The heterogeneity of the mitochondrial population is governed by diffusive transport and inter-unit exchange of proteins, lipids, ions, and RNA within these networks. We present a unifying framework for the dispersion of material within temporal networks of spatially embedded units that span across a broad connectivity range. Specifically, we consider filling of the networks with a locally produced but globally consumed material, demonstrating that the steady-state content is determined by the balance of timescales for spatial encounter between clusters, local fusion, fission, and diffusive transport within a cluster. As the connectivity increases, filling behavior transitions from three-dimensional spread through a `social network' limited by cluster interactions to low-dimensional transport through a largely stationary `physical network' limited by material diffusivity. We extract parameters for mitochondrial networks in three human cell lines, demonstrating that different cells can access both the social and the physical network regimes. These results provide a quantitative basis for predicting the homogenization of biomolecules through a mitochondrial population. Our framework unifies a variety of temporal network structures into an overarching theory for transport through populations of interacting and interconnected units.

physics.bio-ph↗

arXiv2025

Encounter Times of Intermittently Running Particles

Intracellular processes often rely on the timely encounter of mobile reaction partners, including intermittently motor-driven organelles. The underlying cytoskeletal network presents a complex landscape that both directs particle movement and introduces quenched disorder through filament organization. We investigate the mean first encounter times for pairs of intermittently processive and diffusive particles, moving in two dimensions with and without a fixed filament network. In unstructured domains, increasing particle run-length enhances exploration of the domain, but tends to slow down the encounter times compared to equivalent diffusing particles. Encounters for long-running particles occur preferentially near the periphery, contrasting with bulk encounters for the purely diffusive case. When particles are unbiased in their runs along dense filament networks, encounters are shown to be well approximated by a continuum run-and-tumble model. For biased particles, regions of convergent filament orientation can serve as traps that slow the overall spatial exploration but can allow for faster encounter rates by funneling particles into regions of reduced dimensionality. These findings provide a framework for estimating intracellular encounter kinetics, highlighting the role of key physical features such as the effective diffusivity, run times, and network architecture.

physics.bio-ph↗

arXiv2024

Clustering and spatial distribution of mitochondria in dendritic trees

Neuronal dendrites form densely branched tree architectures through which mitochondria must be distributed to supply the cell's energetic needs. Dendritic mitochondria circulate through the tree, undergoing fusion and fission to form clusters of varying sizes. We present a mathematical model for the distribution of such actively-driven particles in a branched geometry. Our model demonstrates that `balanced' trees (wherein cross-sectional area is conserved across junctions and thicker branches support more bushy subtrees) enable symmetric yet distally enriched particle distributions and promote dispersion into smaller clusters. These results highlight the importance of tree architecture and radius-dependent fusion in governing the distribution of neuronal mitochondria.

physics.bio-ph↗

arXiv2023

ER network heterogeneity guides diffusive transport and kinetics

The endoplasmic reticulum (ER) is a dynamic network of interconnected sheets and tubules that orchestrates the distribution of lipids, ions, and proteins throughout the cell. The impact of its complex, dynamic morphology on its function as an intracellular transport hub remains poorly understood. To elucidate the functional consequences of ER network structure and dynamics, we quantify how the heterogeneity of the peripheral ER in COS7 cells affects diffusive protein transport. In vivo imaging of photoactivated ER membrane proteins demonstrates their non-uniform spreading to adjacent regions, in a manner consistent with simulations of diffusing particles on extracted network structures. Using a minimal network model to represent tubule rearrangements, we demonstrate that ER network dynamics are sufficiently slow to have little effect on diffusive protein transport. Furthermore, stochastic simulations reveal a novel consequence of ER network heterogeneity: the existence of 'hot spots' where sparse diffusive reactants are more likely to find one another. Intriguingly, ER exit sites are disproportionately found in these highly accessible regions. Combining in vivo experiments with analytic calculations, quantitative image analysis, and computational modeling, we demonstrate how structure guides diffusive protein transport and reactions in the ER.

physics.bio-ph↗

arXiv2022

Diffusive Exit Rates Through Pores in Membrane-Enclosed Structures

The function of many membrane-enclosed intracellular structures relies on release of diffusing particles that exit through narrow pores or channels in the membrane. The rate of release varies with pore size, density, and length of the channel. We propose a simple approximate model, validated with stochastic simulations, for estimating the effective release rate from cylinders, and other simple-shaped domains, as a function of channel parameters. The results demonstrate that, for very small pores, a low density of channels scattered over the boundary is sufficient to achieve substantial rates of particle release. Furthermore, we show that increasing the length of passive channels will both reduce release rates and lead to a less steep dependence on channel density. Our results are compared to previously-measured local calcium release rates from tubules of the endoplasmic reticulum, providing an estimate of the relevant channel density responsible for the observed calcium efflux.

physics.bio-ph↗

arXiv2021

Diffusive search and trajectories on spatial networks: a propagator approach

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.

physics.bio-ph↗

arXiv2019

Thermal Fracture Kinetics of Heterogeneous Semiflexible Polymers

The fracture and severing of polymer chains plays a critical role in the failure of fibrous materials and the regulated turnover of intracellular filaments. Using continuum wormlike chain models, we investigate the fracture of semiflexible polymers via thermal bending fluctuations, focusing on the role of filament flexibility and dynamics. Our results highlight a previously unappreciated consequence of mechanical heterogeneity in the filament, which enhances the rate of thermal fragmentation particularly in cases where constraints hinder the movement of the chain ends. Although generally applicable to semiflexible chains with regions of different bending stiffness, the model is motivated by a specific biophysical system: the enhanced severing of actin filaments at the boundary between stiff bare regions and mechanically softened regions that are coated with cofilin regulatory proteins. The results presented here point to a potential mechanism for disassembly of filament networks in general and cytoskeletal actin networks in particular by the introduction of locally softened chain regions, as occurs with cofilin binding.

cond-mat.stat-mech↗

arXiv2017

Multi-modal transport and dispersion of organelles in narrow tubular cells

Intracellular components explore the cytoplasm via active motor-driven transport in conjunction with passive diffusion. We model the motion of organelles in narrow tubular cells using analytical techniques and numerical simulations to study the efficiency of different transport modes in achieving various cellular objectives. Our model describes length and time scales over which each transport mode dominates organelle motion, along with various metrics to quantify exploration of intracellular space. For organelles that search for a specific target, we obtain the average capture time for given transport parameters and show that diffusion and active motion contribute comparably to target capture in the biologically relevant regime. Because many organelles have been found to tether to microtubules when not engaged in active motion, we study the interplay between immobilization due to tethering and increased probability of active transport. We derive parameter-dependent conditions under which tethering enhances long range transport and improves the target capture time. These results shed light on the optimization of intracellular transport machinery and provide experimentally testable predictions for the effects of transport regulation mechanisms such as tethering.

physics.bio-ph↗