Simulation of defects, flexibility and rupture in biopolymer networks

We use a coarse grained polymer model and a simple graph representation to introduce defects into a biopolymer network, then cause them to rupture.

Emergent Collective Locomotion in an Active Polymer Model of Entangled Worm Blobs

Numerous worm and arthropod species form physically-connected aggregations in which interactions among individuals give rise to emergent macroscale dynamics and functionalities that enhance collective survival. In particular, some aquatic worms such as the California blackworm (Lumbriculus variegatus) entangle their bodies into dense blobs to shield themselves against external stressors and preserve moisture in dry conditions. Motivated by recent experiments revealing emergent locomotion in blackworm blobs, we investigate the collective worm dynamics by modeling each worm as a self-propelled Brownian polymer. Though our model is two-dimensional, compared to real three-dimensional worm blobs, we demonstrate how a simulated blob can collectively traverse temperature gradients via the coupling between the active motion and the environment. By performing a systematic parameter sweep over the strength of attractive forces between worms, and the magnitude of their directed self-propulsion, we obtain a rich phase diagram which reveals that effective collective locomotion emerges as a result of finely balancing a tradeoff between these two parameters. Our model brings the physics of active filaments into a new meso- and macroscale context and invites further theoretical investigation into the collective behavior of long, slender, semi-flexible organisms.

Minimalistic 3D Chromatin Models: Sparse Interactions in Single Cells Drive the Chromatin Fold and Form Many-Body Units

Computational modeling of 3D chromatin plays an important role in understanding the principles of genome organization. We discuss methods for modeling 3D chromatin structures, with focus on a minimalistic polymer model which inverts population Hi-C into high-resolution, high-coverage single-cell chromatin conformations. Utilizing only basic physical properties such as nuclear volume and no adjustable parameters, this model uncovers a few specific Hi-C interactions (15-35 for enhancer-rich loci in human cells) that can fold chromatin into individual conformations consistent with single-cell imaging, Dip-C, and FISH-measured genomic distance distributions. Aggregating an ensemble of conformations also reproduces population Hi-C interaction frequencies. Furthermore, this single-cell modeling approach allows quantification of structural heterogeneity and discovery of specific many-body units of chromatin interactions. This minimalistic 3D chromatin polymer model has revealed a number of insights: 1) chromatin scaling rules are a result of volume-confined polymers; 2) TADs form as a byproduct of 3D chromatin folding driven by specific interactions; 3) chromatin folding at many loci is driven by a small number of specific interactions; 4) cell subpopulations equipped with different chromatin structural scaffolds are developmental stage-dependent; and 5) characterization of the functional landscape and epigenetic marks of many-body units which are simultaneously spatially co-interacting within enhancer-rich, euchromatic regions. The implications of these findings in understanding the genome structure-function relationship are also discussed.

Emergent collective locomotion in an active polymer model of entangled worm blobs

Numerous worm and arthropod species form physically-connected aggregations in which interactions among individuals give rise to emergent macroscale dynamics and functionalities that enhance collective survival. In particular, some aquatic worms such as the California blackworm (Lumbriculus variegatus) entangle their bodies into dense blobs to shield themselves against external stressors and preserve moisture in dry conditions. Motivated by recent experiments revealing emergent locomotion in blackworm blobs, we investigate the collective worm dynamics by modeling each worm as a self-propelled Brownian polymer. Though our model is two-dimensional, compared to real three-dimensional worm blobs, we demonstrate how a simulated blob can collectively traverse temperature gradients via the coupling between the active motion and the environment. By performing a systematic parameter sweep over the strength of attractive forces between worms, and the magnitude of their directed self-propulsion, we obtain a rich phase diagram which reveals that effective collective locomotion emerges as a result of finely balancing a tradeoff between these two parameters. Our model brings the physics of active filaments into a new meso- and macroscale context and invites further theoretical investigation into the collective behavior of long, slender, semi-flexible organisms.

Generation of dynamic three-dimensional genome structure through phase separation of chromatin

Three-dimensional genome organization plays a critical role in DNA function. Flexible chromatin structure suggested that the genome is phase-separated to form A/B compartments in interphase nuclei. Here, we examined this hypothesis by developing a polymer model of the whole genome of human cells and assessing the impact of phase separation on genome structure. Upon entry to the G1 phase, the simulated genome expanded according to heterogeneous repulsion among chromatin chains, which moved chromatin heterogeneously, inducing phase separation. This repulsion-driven phase separation quantitatively reproduces the experimentally observed chromatin domains, A/B compartments, lamina-associated domains, and nucleolus-associated domains, consistently explaining nuclei of different human cells and predicting their dynamic fluctuations. We propose that phase separation induced by heterogeneous repulsive interactions among chromatin chains largely determines dynamic genome organization.

Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics

Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we present a novel approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observe viscoelastic displacements over microns within minutes in response to near-picoNewton forces, which are well captured by a Rouse polymer model. Our results highlight the fluidity of chromatin, with a moderate contribution of the surrounding material, revealing the minor role of crosslinks and topological effects and challenging the view that interphase chromatin is a gel-like material. Our new technology opens avenues for future research, from chromosome mechanics to genome functions.