arXiv subjects

Andrew D Rutenberg

Publications and source records attributed to Andrew D Rutenberg.

5 recordsLinked to original sources

arXiv2021

Non-Fickian single-file pore transport

Single file diffusion (SFD) exhibits anomalously slow collective transport when particles are able to immobilize by binding and unbinding to the one-dimensional channel within which the particles diffuse. We have explored this system for short pore-like channels using a symmetric exclusion process (SEP) with fully stochastic dynamics. We find that for shorter channels, a non-Fickian regime emerges for slow binding kinetics. In this regime the average flux $\langle Φ\rangle \sim 1/L^3$, where $L$ is the channel length in units of the particle size. We find that a two-state model describes this behavior well for sufficiently slow binding rates, where the binding rates determine the switching time between high-flux bursts of directed transport and low-flux leaky states. Each high-flux burst is Fickian with $\langle Φ\rangle \sim 1/L$. Longer systems are more often in a low flux state, leading to the non-Fickian behavior.

cond-mat.stat-mech↗

arXiv2017

A model of autophagy size selectivity by receptor clustering on peroxisomes

Selective autophagy must not only select the correct type of organelle, but also must discriminate between individual organelles of the same kind so that some but not all of the organelles are removed. We propose that physical clustering of autophagy receptor proteins on the organelle surface can provide an appropriate all-or-none signal for organelle degradation. We explore this proposal using a computational model restricted to peroxisomes and the relatively well characterized pexophagy receptor proteins NBR1 and p62. We find that larger peroxisomes nucleate NBR1 clusters first and lose them last through competitive coarsening. This results in significant size-selectivity that favors large peroxisomes, and can explain the increased catalase signal that results from siRNA inhibition of p62. Excess ubiquitin, resulting from damaged organelles, suppresses size-selectivity but not cluster formation. Our proposed selectivity mechanism thus allows all damaged organelles to be degraded, while otherwise selecting only a portion of organelles for degradation.

physics.bio-ph↗

arXiv2016

Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils

Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development. From the lack of new fibril formation after birth, we further require that the concentration of diffusing precursors stays below the critical concentration for fibril nucleation. We find that the combination of the diffusive bound, which requires larger concentrations to ensure homogeneous fibril radii, and lack of nucleation, which requires lower concentrations, is only marginally consistent with fully-processed collagen using conservative bounds. More realistic bounds may leave no consistent concentrations. Therefore, we propose that unprocessed pC-collagen diffuses from the bundle periphery followed by local C-proteinase activity and subsequent collagen incorporation at each fibril. We suggest that C-proteinase is localized within bundles, at fibril surfaces, during radial fibrillar growth. The much greater critical concentration of pC-collagen, as compared to fully-processed collagen, then provides broad consistency between homogeneous fibril radii and the lack of fibril nucleation during fibril growth.

q-bio.TO↗

arXiv2014

An equilibrium double-twist model for the radial structure of collagen fibrils

Mammalian tissues contain networks and ordered arrays of collagen fibrils originating from the periodic self-assembly of helical 300 nm long tropocollagen complexes. The fibril radius is typically between 25 to 250 nm, and tropocollagen at the surface appears to exhibit a characteristic twist-angle with respect to the fibril axis. Similar fibril radii and twist-angles at the surface are observed in vitro, suggesting that these features are controlled by a similar self-assembly process. In this work, we propose a physical mechanism of equilibrium radius control for collagen fibrils based on a radially varying double-twist alignment of tropocollagen within a collagen fibril. The free-energy of alignment is similar to that of liquid crystalline blue phases, and we employ an analytic Euler-Lagrange and numerical free energy minimization to determine the twist-angle between the molecular axis and the fibril axis along the radial direction. Competition between the different elastic energy components, together with a surface energy, determines the equilibrium radius and twist-angle at the fibril surface. A simplified model with a twist-angle that is linear with radius is a reasonable approximation in some parameter regimes, and explains a power-law dependence of radius and twist-angle at the surface as parameters are varied. Fibril radius and twist-angle at the surface corresponding to an equilibrium free-energy minimum are consistent with existing experimental measurements of collagen fibrils. Remarkably, in the experimental regime, all of our model parameters are important for controlling equilibrium structural parameters of collagen fibrils.

physics.bio-ph↗

arXiv2013

A storage-based model of heterocyst commitment and patterning in cyanobacteria

When deprived of fixed nitrogen (fN), certain filamentous cyanobacteria differentiate nitrogen-fixing heterocysts. There is a large and dynamic fraction of stored fN in cyanobacterial cells, but its role in directing heterocyst commitment has not been identified. We present an integrated computational model of fN transport, cellular growth, and heterocyst commitment for filamentous cyanobacteria. By including fN storage proportional to cell length, but without any explicit cell-cycle effect, we are able to recover a broad and late range of heterocyst commitment times and we observe a strong indirect cell-cycle effect. We propose that fN storage is an important component of heterocyst commitment and patterning in filamentous cyanobacteria. The model allows us to explore both initial and steady-state heterocyst patterns. The developmental model is hierarchical after initial commitment: our only source of stochasticity is observed growth rate variability. Explicit lateral inhibition allows us to examine $Δ$patS, $Δ$hetN, and $Δ$patN phenotypes. We find that $Δ$patS leads to adjacent heterocysts of the same generation, while $Δ$hetN leads to adjacent heterocysts only of different generations. With a shortened inhibition range, heterocyst spacing distributions are similar to those in experimental $Δ$patN systems. Step-down to non-zero external fixed nitrogen concentrations is also investigated.

physics.bio-ph↗