Biology subjects

Kraeter, M.

Publications and source records attributed to Kraeter, M..

6 recordsLinked to original sources

bioRxiv2026

Impact of chemotherapy on leukocyte stiffness -A longitudinal RT-DC study in a breast cancer patient

BackgroundThe physical properties of leukocytes, such as cell size and stiffness, are critical for their circulation in microcapillary networks where rapid shape changes are required to squeeze through vascular constrictions. Alterations in the cells physical phenotype can promote venous thromboembolism (VTE), a common cause of death in cancer patients receiving chemotherapy. While biochemical VTE predictors are well studied, physical properties of blood cells receive less attention. MethodsUsing real-time deformability cytometry (RT-DC), we monitored for the first time the physical phenotype of leukocytes in a longitudinal study of a breast cancer patient treated with epirubicin/cyclophosphamide (EC) and paclitaxel (Pax). ResultsThe leukocyte counts extracted from RT-DC were in good agreement with standard clinical leukograms and EC had no immediate effect on leukocyte properties. However, Pax caused a significant softening of granulo/monocytes and a stiffening of lymphocytes immediately after administration. Leukocyte size was constant throughout the therapy, but we observed an overall increase in leukocyte stiffness, which was restored to normal values 45 weeks post treatment. ConclusionTaken together, our data reveal chemotherapy-induced specific alterations of leukocyte stiffness potentially critical for microcirculation. Thus, RT-DC measurements can add important, yet currently not available information to VTE prediction in cancer patients.

biophysics↗

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↗

bioRxiv2021

Changes in blood cell deformability in Chorea-Acanthocytosis and effects of treatment with dasatinib or lithium

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investigated blood cell deformability of 5 ChAc patients compared to healthy controls during up to one-year individual off-label treatment with the tyrosine kinases inhibitor dasatinib or several weeks with lithium. Measurements with two microfluidic techniques allowed us to assess RBC deformability under different shear stresses. Furthermore, we characterized leukocyte stiffness at high shear stresses. The results show that blood cell deformability - including both RBCs and leukocytes - in general is altered in ChAc patients compared to healthy donors. Therefore, this study shows for the first time an impairment of leukocyte properties in ChAc. During treatment with dasatinib or lithium, we observe alterations in RBC deformability and a stiffness increase for leukocytes. The hematological phenotype of ChAc patients hints at a reorganization of the cytoskeleton in blood cells which partly explains the altered mechanical properties observed here. These findings highlight the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc.

biophysics↗

bioRxiv2021

De novo identification of universal cell mechanics regulators

Cell mechanical properties determine many physiological functions, such as cell fate specification, migration, or circulation through vasculature. Identifying factors that govern the mechanical properties is therefore a subject of great interest. Here we present a mechanomics approach for establishing links between single-cell mechanical phenotype changes and the genes involved in driving them. We combine mechanical characterization of cells across a variety of mouse and human systems with machine learning-based discriminative network analysis of associated transcriptomic profiles to infer a conserved network module of five genes with putative roles in cell mechanics regulation. We validate in silico that the identified gene markers are universal, trustworthy and specific to the mechanical phenotype across the studied mouse and human systems, and demonstrate experimentally that a selected target, CAV1, changes the mechanical phenotype of cells accordingly when silenced or overexpressed. Our data-driven approach paves the way towards engineering cell mechanical properties on demand to explore their impact on physiological and pathological cell functions.

biophysics↗

bioRxiv2020

HIF2α is a Direct Regulator of Neutrophil Motility

Orchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments. In vivo, the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.

immunology↗

bioRxiv2017

Real-time fluorescence and deformability cytometry - flow cytometry goes mechanics

Cell mechanical characterization has recently approached the throughput of conventional flow cytometers. However, this very sensitive, label-free approach still lacks the specificity of molecular markers. Here we combine real-time 1D-imaging fluorescence and deformability cytometry (RT-FDC) to merge the two worlds in one instrument -- opening many new research avenues. We demonstrate its utility using sub-cellular fluorescence localization to identify mitotic cells and test for their mechanical changes in an RNAi screen.

biophysics↗