Biology subjects

Taubenberger, A.

Publications and source records attributed to Taubenberger, A..

6 recordsLinked to original sources

bioRxiv2026

Mapping 3D cellular mechanical activity with matrix-embedded DNA force-history probes

Cells continuously integrate mechanical cues from the surrounding extracellular matrix to control fundamental biological processes such as proliferation and migration. Yet, studying the mechanical activity of cells in 3D over time is challenging, low-throughput, and requires specialized equipment. Here, we introduce DNA-based force-history probes, which convert transient pico-Newton forces into cumulative fluorescent signals within a mechanically adjustable DNA-crosslinked cell culture matrix. The probes provide control over signal lifetimes, allowing stress patterns to be recorded over minutes to days with tunable temporal memory. We use this system to visualize the mechanical activity of breast cancer spheroids and map the trajectories of migrating cancer cells. By combining different fluorophores and DNA-encoded signal lifetimes, we produce dual-color probes that associate temporal information to mechanical events. Overall, force-history probes provide an endpoint-readable record of mechanical cell-matrix activity, offering new opportunities for studying cell function in physiology and disease.

bioengineering↗

bioRxiv2025

A transient mechanical crosstalk between Adherens Junctions and Focal Adhesions sustains cell proliferation in premalignant breast epithelial cells

The weakening of Adherens Junctions (AJs) and Focal Adhesions (FAs) adhesiveness has been proposed to enable the initiation and progression of several types of cancer. Here we report that, prior to disassembling AJs and acquiring malignant traits, premalignant mammary epithelial cells overactivating the Src proto-oncogene transiently enhance tensile forces at both AJs and FAs, thereby gaining a proliferative advantage. We show that AJs and FAs are transiently under higher tensile forces in premalignant Src-activated cells. Cells unable to increase tensile forces at FAs by knocking down PXN or inhibiting FAK activity fail to transiently build up tensile force at AJs and to grow. Conversely, preventing AJ strengthening using EGTA or small interference RNA against P-cadherin suppresses the transient increase in tensile forces at FAs, EGFR-ERK and MRTF-A-SRF activation and cell proliferation. Moreover, knocking down E-cadherin, the sole classical cadherin in Drosophila, inhibits Src-induce tissue overgrowth in vivo. Thus, prior to the loss of cell-cell and cell-matrix adhesiveness, strengthening of AJs and FAs may be an essential early step for mammary cells to gain a proliferative advantage and establish the mechanical and signaling conditions necessary for subsequent malignant transformation. Statement of SignificanceAlthough the weakening of cell-cell and cell-matrix adhesiveness is commonly associated with cancer initiation and progression, our findings reveal that an initial increase in adhesiveness enables proliferation and malignant progression.

cancer biology↗

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↗

bioRxiv2019

EMT-induced cell mechanical changes enhance mitotic rounding strength

To undergo mitosis successfully, most animal cells need to acquire a round shape to provide space for the mitotic spindle. This mitotic rounding relies on mechanical deformation of surrounding tissue and is driven by forces emanating from actomyosin contractility. Cancer cells are able to maintain successful mitosis in mechanically challenging environments such as the increasingly crowded environment of a growing tumor, thus, suggesting an enhanced ability of mitotic rounding in cancer. Here, we show that epithelial mesenchymal transition (EMT), a hallmark of cancer progression and metastasis, gives rise to cell-mechanical changes in breast epithelial cells. These changes are opposite in interphase and mitosis and correspond to an enhanced mitotic rounding strength. Furthermore, we show that cell-mechanical changes correlate with a strong EMT-induced change in the activity of Rho GTPases RhoA and Rac1. Accordingly, we find that Rac1 inhibition rescues the EMT-induced cortex-mechanical phenotype. Our findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as a growing tumor.

biophysics↗

bioRxiv2018

Spheroid culture of mesenchymal stromal cells results in morpho-rheological properties appropriate for improved microcirculation

Human bone marrow mesenchymal stromal cells (MSCs) have been used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networks. Here, we hypothesize that traditional twodimensional (2D) plastic-adherent cell expansion fails to result in appropriate morphorheological properties required for cell-circulation. To address this issue, we adapted a novel method to culture MSCs in non-adherent three-dimensional (3D) spheroids (mesenspheres). The biological properties of mesensphere-cultured MSCs remained identical to conventional 2D cultures. Morpho-rheological analyses revealed a smaller size and lower cell stiffness of mesensphere-derived MSCs compared to plastic-adherent MSCs, measured using real-time deformability cytometry (RT-DC) and atomic force microscopy, resulting in an increased ability to pass through micro-constrictions in an ex vivo microcirculation assay. This ability was confirmed in vivo by analysis of cell accumulation in various organ capillary networks after intravenous injection of mesensphere-derived MSCs in mouse. Our findings generally identify cellular morpho-rheological properties as attractive targets to improve microcirculation and specifically suggest mesensphere cultures as a promising approach for optimized MSC-based therapies.

biophysics↗

bioRxiv2018

Standardized microgel beads as elastic cell mechanical probes

Cell mechanical measurements are gaining increasing interest in biological and biomedical studies. However, there are no standardized calibration particles available that permit the cross-comparison of different measurement techniques operating at different stresses and time-scales. Here we present the rational design, production, and comprehensive characterization of poly-acylamide (PAAm) microgel beads mimicking biological cells. We produced mono-disperse beads at rates of 20 - 60 kHz by means of a microfluidic droplet generator, where the pre-gel composition was adjusted to tune the beads elasticity in the range of cell and tissue relevant mechanical properties. We verified bead homogeneity by optical diffraction tomography and Brillouin microscopy. Consistent elastic behavior of microgel beads at different shear rates was confirmed by AFM-enabled nanoindentation and real-time deformability cytometry (RT-DC). The remaining inherent variability in elastic modulus was rationalized using polymer theory and effectively reduced by sorting based on forward-scattering using conventional flow cytometry. Our results show that PAAm microgel beads can be standardized as mechanical probes, to serve not only for validation and calibration of cell mechanical measurements, but also as cell-scale stress sensors.\n\nSignificance StatementOften vastly different cell mechanical properties are reported even for the same cell type when employing different measurement techniques. This discrepancy shows the urgent need for standardized calibration particles to cross-compare and validate techniques. Microgel beads can serve this purpose, but they have to fulfil specific requirements such as homogeneity, sizes and elasticities in the range of the cells, and they have to provide comparable results independent of the method applied. Here we demonstrate the standardized production of polyacrylamide microgel beads with all the features an elastic cell-mimic should have. These can not only be used as method calibration particles, but can also serve as cell-scale sensors to quantify normal and shear stresses exerted by other cells and inside tissues, enabling many new applications.

biophysics↗