Beck, R. J. | Search bioRxiv

bioRxiv2025

Micromechanical characterisation of osteoarthritic subchondral bone by micropillar compression

Osteoarthritis (OA) is a multifaceted joint disease which poses significant socioeconomic burdens and remains a significant clinical challenge. Evidence suggests that structural and mechanical changes in subchondral bone influence the pathogenesis and development of OA, leading to diminished bone quality and cartilage degeneration. While changes in microstructure and tissue scale elastic properties are well reported, the tissue yield response of subchondral bone in OA and their correlation with compositional changes have not been investigated. Here, we performed quasistatic micropillar compression and nanoindentation within the subchondral bone plate and trabeculae of hydrated non-diseased (ND) and OA affected specimens retrieved from the distal tibia in vivo. The micropillars, extracted by laser ablation, exhibited a taper angle which mandated the use of an in silico micropillar compression routine to back-calculate elastic modulus and strength of the bone tissue that comprised each micropillar. Elastic modulus remained unchanged between ND and OA subchondral bone, whereas strength increased from 46.0 MPa to 57.3 MPa in OA subchondral trabecular bone but not in the bone plate. Micropillar matched Raman spectroscopy and quantitative backscattered electron imaging revealed mineralisation is the underlying determinant of elastic modulus and strength at the microscale. By combining micromechanical and tissue compositional analyses, we investigated how the mechanical properties are related and how these properties are affected in subchondral bone by OA. Our results may be of value in the development and optimisation of interventions used to alleviate the socioeconomic burdens associated with this debilitating joint disease. Statement of significanceOsteoarthritis imposes significant socioeconomic burden, necessitating ever improving treatment strategies. Abnormal mechanical forces at the joint, such as injury, overloading, or aging are associated with osteoarthritis development. While healthy tissue is well understood, the impact of diseases on tissue mechanical properties needs to be brought on a similar level of understanding. We present in this study the first use of micropillar compression for assessing the tissue scale compressive strength of subchondral bone in osteoarthritis. Strength was increased in osteoarthritis compared to non-diseased tissue only in trabeculae subjacent to the bone plate. Compositional analysis confirmed mineralisation as a key determinant of tissue mechanical properties. This integration of micromechanical and compositional analyses sheds light on tissue properties and how these are affected by osteoarthritis in subchondral bone.

bioengineering↗

bioRxiv2025

CLONEID: A Framework for Monitoring and Steering Subclonal Dynamics

Molecular assays can resolve clonal structure, but they are expensive and typically sparse in time, whereas phenotypic observations such as imaging can be collected frequently but often are not preserved in the context needed for later interpretation. We present CLONEID, an event-based framework for organizing clone-resolved phenotypic, molecular, and specimen-context records so that genotype-to-phenotype interpretation can be maintained across time. CLONEID links time-stamped Events, assay-specific Perspectives, and reconciled Identities through structured ingestion, provenance-aware retrieval, and reproducible export, complementing upstream clone-calling methods. In a long-term gastric cancer density-selection experiment, CLONEID linked repeated culture events, growth measurements, and late karyotypic profiling within a shared record, supporting longitudinal interpretation of phenotypic adaptation together with underlying chromosomal state.

bioinformatics↗

bioRxiv2023

Local Adapative Mapping of Karyotype Fitness Landscapes

Despite its critical role in tumor evolution, a detailed quantitative understanding of the evolutionary dynamics of aneuploidy remains elusive. Here we introduce ALFA-K (Adaptive Local Fitness landscapes for Aneuploid Karyotypes), a novel method that infers chromosome-level karyotype fitness landscapes from longitudinal single-cell data. ALFA-K estimates fitness of thousands of karyotypes closely related to observed populations, enabling robust prediction of emergent karyotypes not yet experimentally detected. We validated ALFA-Ks performance using synthetic data from an agent-based model and empirical data from in vitro and in vivo passaged cell lines. Analysis of fitted landscapes suggests several key insights: (1) Whole genome doubling facilitates aneuploidy evolution by narrowing the spectrum of deleterious copy number alterations (CNAs); (2) Environmental context and cisplatin treatment significantly modulate the fitness impact of these alterations; (3) Fitness consequences of CNAs are contingent upon parental karyotype; and (4) Chromosome mis-segregation rates strongly influence the predominant karyotypes in evolving populations.

cancer biology↗