Dynamics, scaling behavior, and control of nuclear wrinkling

The cell nucleus is enveloped by a complex membrane, whose wrinkling has been implicated in disease and cellular aging. The biophysical dynamics and spectral evolution of nuclear wrinkling during multicellular development remain poorly understood due to a lack of direct quantitative measurements. Here, we combine live-imaging experiments, theory, and simulations to characterize the onset and dynamics of nuclear wrinkling during egg development in the fruit fly, Drosophila melanogaster, when nurse cell nuclei increase in size and display stereotypical wrinkling behavior. A spectral analysis of three-dimensional high-resolution data from several hundred nuclei reveals a robust asymptotic power-law scaling of angular fluctuations consistent with renormalization and scaling predictions from a nonlinear elastic shell model. We further demonstrate that nuclear wrinkling can be reversed through osmotic shock and suppressed by microtubule disruption, providing tunable physical and biological control parameters for probing mechanical properties of the nuclear envelope. Our findings advance the biophysical understanding of nuclear membrane fluctuations during early multicellular development.Comment: Main text: 10 pages, 3 figures. SI: 19 pages, 10 figures, 1 tabl

Stationary shapes of deformable particles moving at low Reynolds numbers

Lecture Notes of the Summer School ``Microswimmers -- From Single Particle Motion to Collective Behaviour'', organised by the DFG Priority Programme SPP 1726 (Forschungszentrum J{\"{u}}lich, 2015).Comment: Pages C7.1-16 of G. Gompper et al. (ed.), Microswimmers - From Single Particle Motion to Collective Behaviour, Lecture Notes of the DFG SPP 1726 Summer School 2015, Forschungszentrum J\"ulich GmbH, Schriften des Forschungszentrums J\"ulich, Reihe Key Technologies, Vol 110, ISBN 978-3-95806-083-

Self-organized shape dynamics of active surfaces

Mechanochemical processes in thin biological structures, such as the cellular cortex or epithelial sheets, play a key role during the morphogenesis of cells and tissues. In particular, they are responsible for the dynamical organization of active stresses that lead to flows and deformations of the material. Consequently, advective transport redistributes force-generating molecules and thereby contributes to a complex mechanochemical feedback loop. It has been shown in fixed geometries that this mechanism enables patterning, but the interplay of these processes with shape changes of the material remains to be explored. In this work, we study the fully self-organized shape dynamics using the theory of active fluids on deforming surfaces and develop a numerical approach to solve the corresponding force and torque balance equations. We describe the spontaneous generation of nontrivial surface shapes, shape oscillations, and directed surface flows that resemble peristaltic waves from self-organized, mechanochemical processes on the deforming surface. Our approach provides opportunities to explore the dynamics of self-organized active surfaces and can help to understand the role of shape as an integral element of the mechanochemical organization of morphogenetic processes

Self-organized shape dynamics of active surfaces

Mechanochemical processes in thin biological structures, such as the cellular cortex or epithelial sheets, play a key role during the morphogenesis of cells and tissues. In particular, they are responsible for the dynamical organization of active stresses that lead to flows and deformations of the material. Consequently, advective transport redistributes force-generating molecules and thereby contributes to a complex mechanochemical feedback loop. It has been shown in fixed geometries that this mechanism enables patterning, but the interplay of these processes with shape changes of the material remains to be explored. In this work, we study the fully self-organized shape dynamics using the theory of active fluids on deforming surfaces and develop a numerical approach to solve the corresponding force and torque balance equations. We describe the spontaneous generation of nontrivial surface shapes, shape oscillations, and directed surface flows that resemble peristaltic waves from self-organized, mechanochemical processes on the deforming surface. Our approach provides opportunities to explore the dynamics of self-organized active surfaces and can help to understand the role of shape as an integral element of the mechanochemical organization of morphogenetic processes

Minimal Model of Cellular Symmetry Breaking.

The cell cortex, a thin film of active material assembled below the cell membrane, plays a key role in cellular symmetry-breaking processes such as cell polarity establishment and cell division. Here, we present a minimal model of the self-organization of the cell cortex that is based on a hydrodynamic theory of curved active surfaces. Active stresses on this surface are regulated by a diffusing molecular species. We show that coupling of the active surface to a passive bulk fluid enables spontaneous polarization and the formation of a contractile ring on the surface via mechanochemical instabilities. We discuss the role of external fields in guiding such pattern formation. Our work reveals that key features of cellular symmetry breaking and cell division can emerge in a minimal model via general dynamic instabilities

Attachment of the blastoderm to the vitelline envelope affects gastrulation of insects

During gastrulation, physical forces reshape the simple embryonic tissue to form the complex body plans of multicellular organisms(1). These forces often cause large-scale asymmetric movements of the embryonic tissue(2,3). In many embryos, the gastrulating tissue is surrounded by a rigid protective shell(4). Although it is wellrecognized that gastrulation movements depend on forces that are generated by tissue-intrinsic contractility(5,6), it is not known whether interactions between the tissue and the protective shell provide additional forces that affect gastrulation. Here we show that a particular part of the blastoderm tissue of the red flour beetle (Tribolium castaneum) tightly adheres in a temporally coordinated manner to the vitelline envelope that surrounds the embryo. This attachment generates an additional force that counteracts tissueintrinsic contractile forces to create asymmetric tissue movements. This localized attachment depends on an alpha PS2 integrin (inflated), and the knockdown of this integrin leads to a gastrulation phenotype that is consistent with complete loss of attachment. Furthermore, analysis of another integrin (the alpha PS3 integrin, scab) in the fruit fly (Drosophila melanogaster) suggests that gastrulation in this organism also relies on adhesion between the blastoderm and the vitelline envelope. Our findings reveal a conserved mechanism through which the spatiotemporal pattern of tissue adhesion to the vitelline envelope provides controllable, counteracting forces that shape gastrulation movements in insects

High-throughput cell mechanical phenotyping for label-free titration assays of cytoskeletal modifications

The mechanical fingerprint of cells is inherently linked to the structure of the cytoskeleton and can serve as a label-free marker for cell homeostasis or pathologic states. How cytoskeletal composition affects the physical response of cells to external loads has been intensively studied with a spectrum of techniques, yet quantitative and statistically powerful investigations in the form of titration assays are hampered by the low throughput of most available methods. In this study, we employ real-time deformability cytometry (RT-DC), a novel microfluidic tool to examine the effects of biochemically modified F-actin and microtubule stability and nuclear chromatin structure on cell deformation in a human leukemia cell line (HL60). The high throughput of our method facilitates extensive titration assays that allow for significance assessment of the observed effects and extraction of half-maximal concentrations for most of the applied reagents. We quantitatively show that integrity of the F-actin cortex and microtubule network dominate cell deformation on millisecond timescales probed with RT-DC. Drug-induced alterations in the nuclear chromatin structure were not found to consistently affect cell deformation. The sensitivity of the high-throughput cell mechanical measurements to the cytoskeletal modifications we present in this study opens up new possibilities for label-free dose-response assays of cytoskeletal modifications