Lebhardt, P. | Search bioRxiv

bioRxiv2025

Quantitative phase deformability cytometry (QP-DC) for precise and clinically relevant multiparametric immune cell profiling

Imaging flow cytometry enables the detailed analysis of cell morphology and internal structures through high-throughput cell imaging, and quantitative phase imaging (QPI)-based microfluidic approaches have extended this by providing label-free measures such as dry mass and refractive index (RI). Building on these developments, we present quantitative phase deformability cytometry (QP-DC), which integrates QPI with deformability cytometry to simultaneously measure morphology, mechanics, and intrinsic biophysical parameters such as mass density and dry mass. Numerical refocusing ensures in-focus images independent of axial position, improving precision in contour detection and feature extraction. Using microspheres and whole blood, we validated QP-DC and then applied it to neutrophils under lipopolysaccharide (LPS) stimulation and from patients with systemic lupus erythematosus (SLE). QP-DC revealed LPS-induced reductions in neutrophil mass density and identified heterogeneous subpopulations in SLE. These results demonstrate the capability of QP-DC for precise biophysical and mechanical characterization, offering significant potential for research and clinical diagnostics.

biophysics↗

bioRxiv2025

Individual differences drive social hierarchies in mouse societies

Social hierarchies structure groups and confer advantages on high-ranking individuals. In mice, individual position in hierarchies may emerge situationally from current group compositions, or, alternatively, may remain largely stable across groups as an internalized feature. Dominance and subordination are expressed in behaviors like tube competitions or agonistic chasing. The interaction of these behaviors in the shaping of social position in larger male mouse groups remains largely unknown. To address these questions, we developed the NoSeMaze, a semi-naturalistic, open-source, modular platform that enables automated long-term tracking of unperturbed groups. Across more than 4,000 mouse-days, hierarchies derived from incidental competitions in the integrated tube tests were non-despotic, transitive, and stable even when group compositions changed. This stability supports an internalized component of competition-based social rank. Chasing was also stable across contexts. Notably, chasing was concentrated among high-ranking individuals, consistent with ongoing negotiation of social rank among individuals at the upper end of the hierarchy. The link between chasing and social rank strengthened in groups with less well-defined rank structure, where mice rely more on aggressive signaling to assert their position. Chasing and social rank were associated with certain dimensions of simultaneously measured physical and cognitive features. In summary, high-dimensional tracking with the NoSeMaze reveals that social position in mice is multifaceted and shaped by stable dimensions of individual behavior that persist across changing social contexts. The approach thus enables longitudinal modeling of individuality and social position as key resilience factors.

neuroscience↗