arXiv subjects

Adam R. Lamson

Publications and source records attributed to Adam R. Lamson.

4 recordsLinked to original sources

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↗

arXiv2023

Using a Fast Adaptive Function Approximator to calculate Protein-Filament Binding Kinetics

The cytoskeleton, consisting of biopolymer filaments, molecular motors, and passive crosslinking proteins, provides the internal structure of cells that facilitate movement, growth, and cell division. Understanding the microscopic motor-filament kinetics and dynamics is essential for comprehending macroscopic behaviors of reconstituted cytoskeletal assemblies, such as self-organized flow and active stress. In this study, we employ an adaptive fast Chebyshev approximator based on tree search and parallel computing to accurately recover the equilibrium distribution of crosslinking proteins. Therefore, it satisfies detailed balance in binding through kinetic Monte Carlo sampling while maintaining cost-effectiveness. Additionally, we offer expandable features, including segregating the simulation process via pre-building and allowing the free-loading of different closed-form formulations of the motor's potential energy. Overall, this research contributes to computational advancement in function approximation and has the potential to better describe the evolution of cytoskeletal active matter.

cond-mat.soft↗

arXiv2023

Interpretable neural architecture search and transfer learning for understanding CRISPR/Cas9 off-target enzymatic reactions

Finely-tuned enzymatic pathways control cellular processes, and their dysregulation can lead to disease. Creating predictive and interpretable models for these pathways is challenging because of the complexity of the pathways and of the cellular and genomic contexts. Here we introduce Elektrum, a deep learning framework which addresses these challenges with data-driven and biophysically interpretable models for determining the kinetics of biochemical systems. First, it uses in vitro kinetic assays to rapidly hypothesize an ensemble of high-quality Kinetically Interpretable Neural Networks (KINNs) that predict reaction rates. It then employs a novel transfer learning step, where the KINNs are inserted as intermediary layers into deeper convolutional neural networks, fine-tuning the predictions for reaction-dependent in vivo outcomes. Elektrum makes effective use of the limited, but clean in vitro data and the complex, yet plentiful in vivo data that captures cellular context. We apply Elektrum to predict CRISPR-Cas9 off-target editing probabilities and demonstrate that Elektrum achieves state-of-the-art performance, regularizes neural network architectures, and maintains physical interpretability.

q-bio.MN↗

arXiv2020

Comparison of explicit and mean-field models of cytoskeletal filaments with crosslinking motors

In cells, cytoskeletal filament networks are responsible for cell movement, growth, and division. Filaments in the cytoskeleton are driven and organized by crosslinking molecular motors. In reconstituted cytoskeletal systems, motor activity is responsible for far-from-equilibrium phenomena such as active stress, self-organized flow, and spontaneous nematic defect generation. How microscopic interactions between motors and filaments lead to larger-scale dynamics remains incompletely understood. To build from motor-filament interactions to predict bulk behavior of cytoskeletal systems, more computationally efficient techniques for modeling motor-filament interactions are needed. Here we derive a coarse-graining hierarchy of explicit and continuum models for crosslinking motors that bind to and walk on filament pairs. We compare the steady-state motor distribution and motor-induced filament motion for the different models and analyze their computational cost. All three models agree well in the limit of fast motor binding kinetics. Evolving a truncated moment expansion of motor density speeds the computation by $10^3$--$10^6$ compared to the explicit or continuous-density simulations, suggesting an approach for more efficient simulation of large networks. These tools facilitate further study of motor-filament networks on micrometer to millimeter length scales.

physics.bio-ph↗