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Biology subjects

Gekle, S.

Publications and source records attributed to Gekle, S..

3 recordsLinked to original sources

Formation of perinuclear actin structures is driven by mechanosensitivity of actin polymerization

Actin filaments are one of the most dynamic components of the cytoskeleton. Their fast polymerization, particularly in regions around the nucleus, allows the cell to react quickly and efficiently to external mechanical stimuli by controling nucleus morphology and position, thereby influencing the chromatin organization and gene transcription. While the biochemical mechanisms of actin polymerization are well known, the question why polymerization happens most prominently in the perinuclear region has so far remained elusive. Here, we develop a computational model for actin network formation whose key ingredients are: (i) a fully resolved orientational distribution of the local filaments, (ii) a strain-dependent depolymerization rate and (iii) active stress generation by actomyosin motors. With only these ingredients and without any ad-hoc assumptions on the spatial distribution of signaling molecules, our physics-based model explains the formation of perinuclear actin structures after mechanical stimulation as observed experimentally. In addition, our model also provides some insight into the role actin plays in positioning the nucleus, as it predicts the occurrence of a re-centering force when the cell nucleus is displaced, in quantitative agreement with experimental observations.

biophysics↗

Predicting cell stress and strain during extrusion bioprinting

Bioprinting of living cells can cause major shape deformations, which may severely affect cell survival and functionality. While the shear stresses occurring during cell flow through the printer nozzle have been quantified to some extent, the extensional stresses occurring as cells leave the nozzle into the free printing strand have been mostly ignored. Here we use Lattice-Boltzmann simulations together with a finite-element based cell model to study cell deformation at the nozzle exit. Our simulation results are in good qualitative agreement with experimental microscopy images. We show that for cells flowing in the center of the nozzle extensional stresses can be significant, while for cells flowing off-center their deformation is dominated by the shear flow inside the nozzle. From the results of these simulations, we develop two simple methods that only require the printing parameters (nozzle diameter, flow rate, bioink rheology) to (i) accurately predict the maximum cell stress occurring during the 3D bioprinting process and (ii) approximately predict the cell strains caused by the elongational flow at the nozzle exit.

biophysics↗

Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher-level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 {micro}m wide microfluidic channel. The fluid shear stress induces large, near ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe1 that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

biophysics↗