About

Corey S. O'Hern is a Professor of Mechanical Engineering at Yale University with additional appointments in Applied Physics, Materials Science, Computational Biology & Biomedical Informatics, and Physics. His research focuses on the statistical mechanics of nonequilibrium systems, glass and jamming transitions in soft matter, computational biology, and protein structure, interactions, and design. He has received several awards including the Ackerman Teaching Award in 2018, was elected a Fellow of the American Physical Society in 2017, and has been recognized with awards from the National Science Foundation. His work involves exploring the fundamental physical principles underlying complex systems, soft matter, and biological structures, contributing significantly to the understanding of material behavior, protein folding, and biological morphogenesis.

Selected publications

• Preserving elastic anisotropy with tessellations of granular packings

  ArXiv.org · 2026-04-13

  articleOpen accessSenior author

  Multiscale periodic metamaterials have been designed for numerous applications, such as impact absorption, acoustic cloaking, photonic band gaps, and mechanical logic gates. This prior work has focused on optimizing mesoscale structure for desired bulk isotropic properties. In contrast, we seek to develop materials with highly anisotropic elastic properties. To quantify elastic anisotropy, we introduce two rotationally invariant, normalized quantities that characterize the anisotropic response to shear and compression, respectively, $A_G$ and $A_C$. We find that typical crystalline solids possess average elastic anisotropy $\overline{A}_G \approx 0.15$ and $\overline{A}_C \approx 0.09$. Compared to atomic crystals, jammed granular materials can attain elastic anisotropies that are several orders of magnitude larger. Since grain rearrangements reduce anisotropy in granular materials, to preserve strong elastic anisotropy, we design tessellated granular materials that consist of multiple connected grain-filled voxels, which limit rearrangements and enable highly anisotropic elastic properties. Bulk granular packings with $N$ grains prepared at pressure $p$ have maximal anisotropy for $pN^2\sim1$ and become isotropic in the large-$pN^2$ limit. We show that homogeneously tessellated granular systems can inherit the elastic response of the constituent voxel configurations with elastic anisotropy up to $100$ times that of crystalline compounds over a range of $pN^2$. We show further methods to tune the elastic anisotropy of tessellations by designing heterogeneously patterned voxel configurations and tessellations that allow large boundary deformations.

  PublisherOA PDF

• Droplet breakup against an isolated obstacle

  Soft Matter · 2026-01-01

  articleOpen access

  Quasi-2D droplets pushed by fluid have predictable breakup behavior against cylindrical obstacles.

  PublisherOA PDFDOI

• SCUDDO: An unsupervised clustering algorithm for single-cell Hi-C maps using diagonal diffusion operators

  Bioinformatics · 2026-05-05

  articleOpen access

  MOTIVATION: Advances in high-throughput chromatin conformation capture have provided insight into the three-dimensional structure and organization of chromatin. While bulk Hi-C experiments capture spatio-temporally averaged chromatin interactions across millions of cells, single-cell Hi-C experiments report on the chromatin interactions of individual cells. Supervised and unsupervised algorithms have been developed to embed single-cell Hi-C maps and identify different cell types. However, single-cell Hi-C maps are often difficult to cluster due to their high sparsity, with state-of-the-art algorithms achieving a maximum Adjusted Rand Index (ARI) of only ≲0.4 on several datasets. RESULTS: We introduce a novel unsupervised algorithm, Single-cell Clustering Using Diagonal Diffusion Operators (SCUDDO), to embed and cluster single-cell Hi-C maps. We evaluate SCUDDO on four previously difficult-to-cluster single-cell Hi-C datasets, and show that it can outperform other current algorithms in ARI by ≳0.2. Further, SCUDDO outperforms all other tested algorithms even when we restrict the number of intrachromosomal maps for each cell type and when we use only a small fraction of contacts in each Hi-C map. Thus, SCUDDO can capture the underlying latent features of single-cell Hi-C maps and provide accurate labelling of cell types even when cell types are not known a priori. AVAILABILITY: SCUDDO is freely available at https://www.github.com/lmaisuradze/scuddo as well as https://doi.org/10.6084/m9.figshare.31759915. The tested datasets are publicly available and can be downloaded from the Gene Expression Omnibus.

  PublisherDOI

• Assessment of scoring functions for computational models of protein-protein interfaces.

  PubMed · 2026-01-07

  articleSenior author

  An important goal of computational studies of protein-protein interfaces (PPIs) is to predict the binding site between two monomers that form a heterodimer. The simplest version of this problem is to rigidly re-dock the bound forms of the monomers, which involves generating computational models of the heterodimer and then scoring them to determine the most native-like models. PPI scoring functions have been assessed previously using rank- and classification-based metrics; however, these methods are sensitive to the number and quality of models in the scoring function training set. We assess the accuracy of seven PPI scoring functions by comparing their scores of computational models of PPIs to a measure of structural similarity to the x-ray crystal structure (i.e. the DockQ score) for a non-redundant set of heterodimers from the Protein Data Bank. For each heterodimer, we generate re-docked models uniformly sampled over DockQ and calculate the Spearman correlation between the PPI scores and DockQ. For some targets, the scores and DockQ are highly correlated; however, for many targets, there are weak correlations. Several physical features explain the difference between difficult- and easy-to-score targets. Strong correlations exist between the score and DockQ for targets with highly intertwined monomers and many interface contacts. We also develop a new score based on only two physical features that matches the performance of current PPI scoring functions. In addition, we address the more general problem of flexible-body docking by generating and docking intermediate monomer conformations between their bound and unbound forms. We score the docked models and find that the Spearman correlations between the PPI scores and DockQ decrease strongly as the monomers are deformed from their bound conformations. These results emphasize that PPI docking predictions can be improved by focusing on correlations between the PPI score and DockQ and incorporating more discriminating physical features into PPI scoring functions.

  Publisher

• Adipose-mimetic granular hydrogels uncover biophysical cues driving breast cancer invasion

  Cell Biomaterials · 2026-03-01

  article
  PublisherDOI

• Preserving elastic anisotropy with tessellations of granular packings

  arXiv (Cornell University) · 2026-04-13

  preprintOpen accessSenior author

  Multiscale periodic metamaterials have been designed for numerous applications, such as impact absorption, acoustic cloaking, photonic band gaps, and mechanical logic gates. This prior work has focused on optimizing mesoscale structure for desired bulk isotropic properties. In contrast, we seek to develop materials with highly anisotropic elastic properties. To quantify elastic anisotropy, we introduce two rotationally invariant, normalized quantities that characterize the anisotropic response to shear and compression, respectively, $A_G$ and $A_C$. We find that typical crystalline solids possess average elastic anisotropy $\overline{A}_G \approx 0.15$ and $\overline{A}_C \approx 0.09$. Compared to atomic crystals, jammed granular materials can attain elastic anisotropies that are several orders of magnitude larger. Since grain rearrangements reduce anisotropy in granular materials, to preserve strong elastic anisotropy, we design tessellated granular materials that consist of multiple connected grain-filled voxels, which limit rearrangements and enable highly anisotropic elastic properties. Bulk granular packings with $N$ grains prepared at pressure $p$ have maximal anisotropy for $pN^2\sim1$ and become isotropic in the large-$pN^2$ limit. We show that homogeneously tessellated granular systems can inherit the elastic response of the constituent voxel configurations with elastic anisotropy up to $100$ times that of crystalline compounds over a range of $pN^2$. We show further methods to tune the elastic anisotropy of tessellations by designing heterogeneously patterned voxel configurations and tessellations that allow large boundary deformations.

  PublisherDOI

• Anisotropic stress history effects in erodible sediment beds

  2025-12-08

  article

  Bedload transport occurs when the shear stress, or non-dimensional Shields stress, imparted by a fluid onto a sediment bed exceeds a critical value for sediment entrainment. The history of fluid stress imparted onto a sediment bed influences this critical Shields stress, with bed strengthening occurring under unidirectional flows and bed weakening occurring when the flow direction is reversed. In this study, we examine directional strengthening and weakening in a sediment bed for multiple fluid stress orientations using a rotating bed of sand in a laboratory flume. This sediment bed is exposed to an initial subcritical conditioning flow followed by a subsequent erosive flow at an offset angle of 0º, 45º, 90º, 135º, or 180º. We identify the particle trajectories of a population of sediment grains to measure their velocity, activity, and associated bulk statistics. We confirm bed strengthening (i.e., lower grain velocity and activity) in the unidirectional case, especially for flows at or below the nominal critical Shields stress. As the angular offset increases between the conditioning and erosive flows, both grain velocity and activity increase, with the greatest bed weakening at offsets of 135° and 180°. Our results confirm that stress history is stored anisotropically in the sediment bed, supporting mechanisms such as shear jamming where an anisotropic granular fabric develops in response to shear. These results inform our understanding of how subcritical and critical fluid-imposed stresses can modify the grain contact and force networks in geophysical contexts.

  PublisherDOI

• Cell Shape Emerges from Motion

  ArXiv.org · 2025-11-18

  preprintOpen accessSenior author

  We perform cell segmentation on images from experimental studies of confluent, mobile cells in epithelial monolayers and show that these systems possess a broad, positively-skewed shape parameter distribution $P(\mathcal{A})$, where $\mathcal{A}=p^2/4πa$, $p$ is the perimeter, and $a$ is area of each cell. $P(\mathcal{A})$ is peaked at a value higher than the typical shape parameter $\mathcal{A}^* \sim 1.15$ that occurs for randomly packed, static confluent cell monolayers. The distribution does not arise from a heterogeneous population of cells with different fixed $\mathcal{A}$, nor can it arise from cell shape fluctuations from strains below the elastic limit. Instead, we find that all cells in each monolayer sample $\mathcal{A}$ values that span the full shape parameter distribution. We develop a deformable particle model that allows cell perimeter to adapt to local forces during cell motion, and this model recovers $P(\mathcal{A})$ to within $5\%$ for both MDCK and HaCaT epithelial cell monolayers. These results emphasize that confluent epithelial monolayers of mobile cells generate a well-defined broad shape parameter distribution that is independent of the initial cell shapes.

  PublisherOA PDFDOI

• Protein Folding as a Jamming Transition

  PRX Life · 2025-03-27 · 3 citations

  preprintOpen accessSenior author

  Proteins fold to a specific functional conformation with a densely packed core that controls their stability. Despite their importance, we lack a quantitative explanation for why all protein cores, regardless of their overall fold, possess the same average packing fraction <a:math xmlns:a="http://www.w3.org/1998/Math/MathML"><a:mrow><a:mo>〈</a:mo><a:mi>ϕ</a:mi><a:mo>〉</a:mo><a:mo>≈</a:mo><a:mn>0.55</a:mn></a:mrow></a:math>. However, important developments in the physics of jamming in particulate systems can shed light on the packing of protein cores. Here, we extend the framework of jamming to describe core packing in collapsed polymers, as well as in all-atom models of folded proteins. First, we show in a spherical bead-spring polymer model (with and without bond-angle constraints) that as the hydrophobic interactions increase relative to thermal fluctuations, a jamming-like transition occurs when the core packing fraction exceeds <b:math xmlns:b="http://www.w3.org/1998/Math/MathML"><b:msub><b:mi>ϕ</b:mi><b:mi>c</b:mi></b:msub></b:math> with the same power-law scaling behavior for the potential energy <c:math xmlns:c="http://www.w3.org/1998/Math/MathML"><c:msub><c:mi>V</c:mi><c:mi>r</c:mi></c:msub></c:math>, excess contact number <d:math xmlns:d="http://www.w3.org/1998/Math/MathML"><d:mrow><d:mi mathvariant="normal">Δ</d:mi><d:mi>N</d:mi></d:mrow></d:math>, and characteristic frequency of the vibrational density of states <f:math xmlns:f="http://www.w3.org/1998/Math/MathML"><f:msup><f:mi>ω</f:mi><f:mo>*</f:mo></f:msup></f:math> versus <g:math xmlns:g="http://www.w3.org/1998/Math/MathML"><g:mrow><g:mi mathvariant="normal">Δ</g:mi><g:mi>ϕ</g:mi><g:mo>=</g:mo><g:mi>ϕ</g:mi><g:mo>−</g:mo><g:msub><g:mi>ϕ</g:mi><g:mi>c</g:mi></g:msub></g:mrow></g:math> as that for jammed particulate systems. Then, we develop an all-atom model for proteins and find that, above <i:math xmlns:i="http://www.w3.org/1998/Math/MathML"><i:mrow><i:msub><i:mi>ϕ</i:mi><i:mi>c</i:mi></i:msub><i:mo>∼</i:mo><i:mn>0.55</i:mn></i:mrow></i:math>, protein cores undergo a jamming-like transition, but with anomalous power-law scaling for <j:math xmlns:j="http://www.w3.org/1998/Math/MathML"><j:msub><j:mi>V</j:mi><j:mi>r</j:mi></j:msub><j:mo>,</j:mo><j:mo> </j:mo><j:mrow><j:mi mathvariant="normal">Δ</j:mi><j:mi>N</j:mi></j:mrow></j:math>, and <l:math xmlns:l="http://www.w3.org/1998/Math/MathML"><l:msup><l:mi>ω</l:mi><l:mo>*</l:mo></l:msup></l:math> versus <m:math xmlns:m="http://www.w3.org/1998/Math/MathML"><m:mrow><m:mi mathvariant="normal">Δ</m:mi><m:mi>ϕ</m:mi></m:mrow></m:math>. The all-atom protein model remains close to the native protein structure during jamming and accurately refolds from partially unfolded states.

  PublisherOA PDFDOI

• Variable Stiffness and Variable Size Particles for Reconfigurable Granular Metamaterials

  2025-04-22

  article

  Soft robots can achieve exceptional adaptability through tunable morphological and mechanical properties. Incorporating materials with dynamically adjustable characteristics can enhance this versatility further. Granular meta-materials, consisting of discrete particles with individually variable properties, offer a promising approach to bulk property adaptation by adjusting the properties of constituent particles. This work introduces variable size and variable stiffness (VS<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup>) particles, in which both particle size and stiffness are independently modulated through concentric pneumatic chambers. We characterize the achievable workspace, mapping particle responses to independent chamber inflation. To demonstrate their use in a granular assembly, we arrange an array of VS<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> particles in a hexagonal packing and validate that behavior in packed configurations aligns with free-space characterizations. This study establishes a foundation for adaptive granular materials and provides a platform for further computational and experimental exploration of 2D and 3D granular metamaterials with tunable properties.

  PublisherDOI

Awards & honors

• Ackerman Teaching Award (2018)
• Elected Fellow of the American Physical Society (2017)
• Cyber-Enabled Discovery and Innovation Award from the Nation…
• Faculty Early Career Development Award from the National Sci…