arXiv subjects

Anna C. Nelson

Publications and source records attributed to Anna C. Nelson.

3 recordsLinked to original sources

arXiv2026

Platelet plug microstructure and flow modulate fibrin gelation dynamics: Insights from computational simulations

During the formation of a thrombus, the architecture of the growing platelet aggregate is heterogeneous, with areas of dense and loosely packed platelets. The surface of activated platelets facilitate biochemical coagulation reactions that ultimately result in the formation of a fibrin network which stabilizes the thrombus. How platelet-plug microstructure and flow jointly govern the onset and development of fibrin is incompletely understood. We developed a novel 2D computational framework that integrates (1) a pre-adhered, discrete platelet aggregate, (2) a reduced coagulation model that generates thrombin, and (3) a fibrin polymerization model. Three platelet-plug configurations were constructed with prescribed interplatelet gaps and simulations were performed with various wall shear rates. We quantified spatiotemporal clotting metrics, including coagulation factor concentrations, fibrin evolution, and gelation onset. Across geometries, gelation initiation accelerated with increasing plug density. For more dense geometries, gelation emerged first near the plug periphery. As the platelet density increased, intraplug transport was increasingly restricted and the thrombin concentrations in between platelets increased. In contrast, the loose plug supported fibrinogen replenishment deeper into the plug core. Despite slower coagulation initiation due to reduced platelet surface area, monomer generation persisted in the interior, causing gelation to begin at the vessel wall. These results suggest a mechanistic tradeoff: rapid sealing of the injured vessel wall by early platelet contraction, i.e. plug densification, may impede the intraplug fibrin formation needed for durable stabilization. The proposed model provides a basis for studies of platelet-coagulation interactions under flow, including therapeutic developments relevant to prevention of cardiovascular disease.

q-bio.BM↗

arXiv2025

Nucleation feedback can drive establishment and maintenance of biased microtubule polarity in neurites

The microtubule cytoskeleton is comprised of dynamic, polarized filaments that facilitate transport within the cell. Polarized microtubule arrays are key to facilitating cargo transport in long cells such as neurons. Microtubules also undergo dynamic instability, where the plus and minus ends of the filaments switch between growth and shrinking phases, leading to frequent microtubule turnover. Although microtubules often completely disassemble and new filaments nucleate, microtubule arrays have been observed to both maintain their biased orientation throughout the cell lifetime and to rearrange their polarity as an adaptive response to injury. Motivated by cytoskeleton organization in neurites, we propose a spatially-explicit stochastic model of microtubule arrays and investigate how nucleation of new filaments could generate biased polarity in a simple linear domain. Using a continuous-time Markov chain model of microtubule growth dynamics, we model and parameterize two experimentally-validated nucleation mechanisms: nucleation feedback, where the direction of filament growth depends on existing microtubule content, and a checkpoint mechanism, where microtubules that nucleate in a direction opposite to the majority experience frequent catastrophe. When incorporating these validated mechanisms into the spatial model, we find that nucleation feedback is sufficient to establish biased polarity in neurites of different lengths, and that the emergence and maintenance of biased polarity is relatively stable in spite of stochastic fluctuations. This work provides a framework to study the relationship between microtubule nucleation and polarity, and could extend to give insights into mechanisms that drive the formation of polarized filament arrays in other biological settings.

q-bio.QM↗

arXiv2025

Emergent microtubule properties in a model of filament turnover and nucleation

Microtubules (MTs) are dynamic protein filaments essential for intracellular organization and transport, particularly in long-lived cells such as neurons. The plus and minus ends of neuronal MTs switch between growth and shrinking phases, and the nucleation of new filaments is believed to be regulated in both healthy and injury conditions. We propose stochastic and deterministic mathematical models to investigate the impact of filament nucleation and length-regulation mechanisms on emergent properties such as MT lengths and numbers in living cells. We expand our stochastic continuous-time Markov chain model of filament dynamics to incorporate MT nucleation and capture realistic stochastic fluctuations in MT numbers and tubulin availability. We also propose a simplified partial differential equation (PDE) model, which allows for tractable analytical investigation into steady-state MT distributions under different nucleation and length-regulating mechanisms. We find that the stochastic and PDE modeling approaches show good agreement in predicted MT length distributions, and that both MT nucleation and the catastrophe rate of large-length MTs regulate MT length distributions. In both frameworks, multiple mechanistic combinations achieve the same average MT length. The models proposed can predict parameter regimes where the system is scarce in tubulin, the building block of MTs, and suggest that low filament nucleation regimes are characterized by high variation in MT lengths, while high nucleation regimes drive high variation in MT numbers. These mathematical frameworks have the potential to improve our understanding of MT regulation in both healthy and injured neurons.

physics.bio-ph↗