Biology subjects

Fürthauer, S.

Publications and source records attributed to Fürthauer, S..

3 recordsLinked to original sources

bioRxiv2025

Centrosome Softening As A Mechanical Adaptation For Mitosis

Centrosomes are microtubule-organizing centers important for mitotic spindle assembly and chromosome segregation. During mitosis, centrosomes are exposed to mechanical forces via the microtubules they nucleate, yet the material properties underlying their response to these forces remain poorly understood. In this study, we systematically probed the mechanical behavior of C. elegans centrosomes, both in vitro and in vivo. Using microtubule perturbations and quantitative live cell imaging, we found that centrosomes become increasingly deformed during mitosis. Centrosome deformation is independent of cortical pulling forces but instead results from microtubule polymerization within the pericentriolar material. This deformation impacts centrosome size: as microtubule number decreases with cell volume in early cleavage divisions, centrosome size scales proportionately. To directly measure centrosome elasticity, we employed atomic force microscopy (AFM) on isolated centrosomes in vitro and Brillouin light scattering microscopy in developing embryos in vivo. Both approaches revealed that centrosomes progressively soften during mitosis. Theoretical modeling predicts that softening serves to dampen spindle force fluctuations, helping to protect kinetochore-microtubule interactions and safeguarding chromosome segregation. Further, softening may enhance centrosomal microtubule nucleation capacity, facilitating mitotic spindle assembly, particularly in large early embryonic cells. We propose that centrosome softening is a mechanical adaptation for mitosis that couples microtubule number to centrosome size through force-dependent deformation. This optimally balances two mitotic requirements: the need for robust microtubule nucleation and the ability to withstand spindle forces, thereby ensuring accurate cell division.

cell biology↗

bioRxiv2022

Active mechanics of sea star oocytes

Cell shape changes, driven by the contractile actomyosin cortex, are essential for multicellular organisms. Yet, how contractility and cell shape changes emerge from molecular scale interactions between proteins in the actomyosin cortex remains unclear. Oocytes of the bat star Patiria miniata exhibit a traveling wave of cellular deformation during meiosis, known as a surface contraction wave (SCW). Here, we exploit this highly stereotypical deformation to study how cortical properties are set by microscale processes. By pharmacologically modulating the levels of polymerized actin, we show that the wildtype composition maximizes the cellular deformation rate. To understand these results, we developed an active fluid model for shape changes that demonstrates that deformation rates are set by the ratio between cortical viscosity and active contractile stresses and provides a framework for deriving these two key material properties from coarse-grained molecular-scale interactions. In this model, the ratio of active stress to viscosity peaks at intermediate admixtures of passive crosslinkers. This explains the observations of the drug treatment experiments and makes additional predictions, namely that overexpression of either myosin or passive crosslinkers would decrease deformation rates, which we verified experimentally. Together, this shows that the interplay between cortical active stress and viscosity relies on balancing the ratio of myosin to passive crosslinkers on each filament, which can be modulated by actin density. Our results argue that changing the relative molecular compositions of cortical crosslinks and motors provides a mechanism that biological systems could exploit for robust and predictable control over both viscosity and active stresses.

biophysics↗

bioRxiv2020

Co-movement of astral microtubules, organelles and F-actin suggests aster positioning by surface forces in frog eggs

How bulk cytoplasm generates forces to separate post-anaphase microtubule (MT) asters in Xenopus laevis and other large eggs remains unclear. Previous models proposed dynein-based organelle transport generates length-dependent forces on astral MTs that pull centrosomes through the cytoplasm, away from the midplane. In Xenopus egg extracts, we co-imaged MTs, endoplasmic reticulum (ER), mitochondria, acidic organelles, F-actin, keratin, and fluorescein in moving and stationary asters. In asters that were moving in response to dynein and actomyosin forces, we observed that all cytoplasmic components moved together, i.e., as a continuum. Dynein-mediated organelle transport was restricted by interior MTs and F-actin. Organelles exhibited a burst of dynein-dependent inward movement at the growing aster surface, then mostly halted inside the aster. Dynein-coated beads were slowed by F-actin, but in contrast to organelles, beads did not halt inside asters. These observations call for new models of aster positioning based on surface forces and internal stresses.

cell biology↗