% Encoding: UTF-8 @COMMENT{BibTeX export based on data in FAU CRIS: https://cris.fau.de/} @COMMENT{For any questions please write to cris-support@fau.de} @article{faucris.205578313, abstract = {Background: An increasingly used behavioral paradigm for the objective assessment of a possible tinnitus percept in animal models has been proposed by Turner and coworkers in 2006. It is based on gap-prepulse inhibition (PPI) of the acoustic startle reflex (ASR) and usually referred to as GPIAS. As it does not require conditioning it became the method of choice to study neuroplastic phenomena associated with the development of tinnitus.Objective:It is still controversial if GPIAS is really appropriate for tinnitus screening, as the hypothesis that a tinnitus percept impairs the gap detection ability ("filling-in interpretation" is still questioned. Furthermore, a wide range of criteria for positive tinnitus detection in GPIAS have been used across different laboratories and there still is no consensus on a best practice for statistical evaluation of GPIAS results. Current approaches are often based on simple averaging of measured PPI values and comparisons on a population level without the possibility to perform valid statistics on the level of the single animal.Methods:A total number of 32 animals were measured using the standard GPIAS paradigm with varying number of measurement repetitions. Based on this data further statistical considerations were performed.Results:We here present a new statistical approach to overcome the methodological limitations of GPIAS. In a first step we show that ASR amplitudes are not normally distributed. Next we estimate the distribution of the measured PPI values by exploiting the full combinatorial power of all measured ASR amplitudes. We demonstrate that the amplitude ratios (1-PPI) are approximately lognormally distributed, allowing for parametrical testing of the logarithmized values and present a new statistical approach allowing for a valid and reliable statistical assessment of PPI changes in GPIAS.Conclusion:Based on our statistical approach we recommend using a constant criterion, which does not systematically depend on the number of measurement repetitions, in order to divide animals into a tinnitus and a non-tinnitus group. In particular, we recommend using a constant threshold based on the effect size as criterion, as the effect size, in contrast to thep-value, does not systematically depend on the number of measurement repetitions.}, author = {Schilling, Achim and Krauß, Patrick and Gerum, Richard and Metzner, Claus and Tziridis, Konstantin and Schulze, Holger}, doi = {10.3389/fnbeh.2017.00198}, faupublication = {yes}, journal = {Frontiers in Behavioral Neuroscience}, note = {EVALuna2:33208}, peerreviewed = {Yes}, title = {{A} {New} {Statistical} {Approach} for the {Evaluation} of {Gap}-prepulse {Inhibition} of the {Acoustic} {Startle} {Reflex} ({GPIAS}) for {Tinnitus} {Assessment}}, volume = {11}, year = {2017} } @article{faucris.107327264, author = {Richter, Sebastian and Gerum, Richard and Schneider, Werner and Fabry, Ben and Le Bohec, Céline and Paranhos Zitterbart, Daniel}, doi = {10.1111/2041-210X.12971}, faupublication = {yes}, journal = {Methods in Ecology and Evolution}, peerreviewed = {unknown}, title = {{A} remote-controlled observatory for behavioural and ecological research: {A} case study on emperor penguins}, volume = {0}, year = {2018} } @article{faucris.216187886, abstract = {Cell migration through the extracellular matrix is governed by the interplay between cell-generated propulsion forces, adhesion forces, and resisting forces arising from the steric hindrance of the matrix. Steric hindrance in turn depends on matrix porosity, matrix deformability, cell size, and cell deformability. In this study, we investigate how cells respond to changes in steric hindrance that arise from altered cell mechanical properties. Specifically, we measure traction forces, cell morphology, and invasiveness of MDA-MB 231 breast cancer cells in three-dimensional collagen gels. To modulate cell mechanical properties, we either decrease nuclear deformability by twofold overexpression of the nuclear protein lamin A or we introduce into the cells stiff polystyrene beads with a diameter larger than the average matrix pore size. Despite this increase of steric hindrance, we find that cell invasion is only marginally inhibited, as measured by the fraction of motile cells and the mean invasion depth. To compensate for increased steric hindrance, cells employ two alternative strategies. Cells with higher nuclear stiffness increase their force polarity, whereas cells with large beads increase their net contractility. Under both conditions, the collagen matrix surrounding the cells stiffens dramatically and carries increased strain energy, suggesting that increased force polarity and increased net contractility are functionally equivalent strategies for overcoming an increased steric hindrance.}, author = {Condor, Mar and Mark, Christoph and Gerum, Richard and Grummel, Nadine and Bauer, Andreas and Garcia-Aznar, Jose M. and Fabry, Ben}, doi = {10.1016/j.bpj.2019.02.029}, faupublication = {yes}, journal = {Biophysical Journal}, note = {CRIS-Team WoS Importer:2019-04-18}, pages = {1305-1312}, peerreviewed = {Yes}, title = {{Breast} {Cancer} {Cells} {Adapt} {Contractile} {Forces} to {Overcome} {Steric} {Hindrance}}, volume = {116}, year = {2019} } @article{faucris.280966242, abstract = {During bioprinting, cells are suspended in a viscous bioink and extruded under pressure through small diameter printing needles. The combination of high pressure and small needle diameter exposes cells to considerable shear stress, which can lead to cell damage and death. Approaches to monitor and control shear stress-induced cell damage are currently not well established. To visualize the effects of printing-induced shear stress on plasma membrane integrity, we add FM 1-43 to the bioink, a styryl dye that becomes fluorescent when bound to lipid membranes, such as the cellular plasma membrane. Upon plasma membrane disruption, the dye enters the cell and also stains intracellular membranes. Extrusion of alginate-suspended NIH/3T3 cells through a 200 mu m printing needle led to an increased FM 1-43 incorporation at high pressure, demonstrating that typical shear stresses during bioprinting can transiently damage the plasma membrane. Cell imaging in a microfluidic channel confirmed that FM 1-43 incorporation is caused by cell strain. Notably, high printing pressure also impaired cell survival in bioprinting experiments. Using cell types of different stiffnesses, we find that shear stress-induced cell strain, FM 1-43 incorporation and cell death were reduced in stiffer compared to softer cell types and demonstrate that cell damage and death correlate with shear stress-induced cell deformation. Importantly, supplementation of the suspension medium with physiological concentrations of CaCl2 greatly reduced shear stress-induced cell damage and death but not cell deformation. As the sudden influx of calcium ions is known to induce rapid cellular vesicle exocytosis and subsequent actin polymerization in the cell cortex, we hypothesize that calcium supplementation facilitates the rapid resealing of plasma membrane damage sites. We recommend that bioinks should be routinely supplemented with physiological concentrations of calcium ions to reduce shear stress-induced cell damage and death during extrusion bioprinting.}, author = {Fischer, Lena and Nosratlo, Mojtaba and Hast, Katharina and Karakaya, Emine and Ströhlein, Nadi and Esser, Tilman and Gerum, Richard and Richter, Sebastian and Engel, Felix and Detsch, Rainer and Fabry, Ben and Thievessen, Ingo}, doi = {10.1088/1758-5090/ac84af}, faupublication = {yes}, journal = {Biofabrication}, note = {CRIS-Team WoS Importer:2022-08-26}, peerreviewed = {Yes}, title = {{Calcium} supplementation of bioinks reduces shear stress-induced cell damage during bioprinting}, volume = {14}, year = {2022} } @article{faucris.227599848, abstract = {Camera images and video recordings are simple and non-invasive tools to investigate animals in their natural habitat. Quantitative evaluations, however, often require an exact reconstruction of object positions, sizes, and distances in the image. Here, we provide an open source software package to perform such calculations. Our approach allows the user to correct for perspective distortion, transform images to “bird's-eye” view projections, or transform image-coordinates to real-world coordinates and vice versa. The extrinsic camera parameters that are necessary to perform such image corrections and transformations (elevation, tilt/roll angle, and heading of the camera) are obtained from the image using contextual information such as a visible horizon, GPS coordinates of landmarks, known object sizes, or images of the same object obtained from different viewing angles. All mathematical operations are implemented in the Python package CameraTransform. The performance of the implementation is evaluated using computer-generated synthetic images with known camera parameters. Moreover, we test our algorithm on images of emperor penguin colonies, and demonstrate that the camera tilt and roll angles can be estimated with an error of less than one degree, and the camera elevation with an error of less than 5%. The CameraTransform software package simplifies camera matrix-based image transformations and the extraction of quantitative image information. An extensive documentation and usage examples in an ecological context are provided at http://cameratransform.readthedocs.io.}, author = {Gerum, Richard and Richter, Sebastian and Winterl, Alexander and Mark, Christoph and Fabry, Ben and Le Bohec, Céline and Paranhos Zitterbart, Daniel}, doi = {10.1016/j.softx.2019.100333}, faupublication = {yes}, journal = {SoftwareX}, keywords = {Camera lens distortions; Geo-referencing; Perspective projection; Quantitative image analysis}, note = {CRIS-Team Scopus Importer:2019-10-08}, peerreviewed = {Yes}, title = {{CameraTransform}: {A} {Python} package for perspective corrections and image mapping}, volume = {10}, year = {2019} } @article{faucris.120195504, author = {Gerum, Richard and Richter, Sebastian and Winterl, Alexander and Fabry, Ben and Paranhos Zitterbart, Daniel}, faupublication = {yes}, journal = {arXiv}, peerreviewed = {No}, title = {{CameraTransform}: a {Scientific} {Python} {Package} for {Perspective} {Camera} {Corrections}}, year = {2017} } @article{faucris.112450844, abstract = {The biocompatibility of commercially pure magnesium-based (cp Mg) biodegradable implants is compromised of strong hydrogen evolution and surface alkalization due to high initial corrosion rates of cp Mg in the physiological environment. To mitigate this problem, the addition of corrosion-retarding alloying elements or coating of implant surfaces has been suggested. In the following work, we explored the effect of organic coatings on long-term cell growth. cp Mg was coated with aminopropyltriehtoxysilane + vitamin C (AV), carbonyldiimidazole (CDI), or stearic acid (SA). All three coatings have been previously suggested to reduce initial corrosion and to enhance protein adsorption and hence cell adhesion on magnesium surfaces. Endothelial cells (DH1+/+) and osteosarcoma cells (MG63) were cultured on coated samples for up to 20 days. To quantify Mg corrosion, electrochemical impedance spectroscopy (EIS) was measured after 1, 3, and 5 days of cell culture. We also investigated the speed of initial cell spreading after seeding using fluorescently labeled fibroblasts (NIH/3T3). Hydrogen evolution after contact with cell culture medium was markedly decreased on AV- and SA-coated Mg compared to uncoated Mg. These coatings also showed improved cell adhesion and spreading after 24 h of culture comparable to tissue-treated plastic surfaces. On AV-coated cp Mg, a confluent layer of endothelial cells formed after 5 days and remained intact for up to 20 days. Together, these data demonstrate that surface coating with AV is a viable strategy for improving long-term biocompatibility of cp Mg-based implants. EIS measurements confirmed that the presence of a confluent cell layer increased the corrosion resistance.}, author = {Wagener, Victoria and Schilling, Achim and Mainka, Astrid and Hennig, Diana and Gerum, Richard and Kelch, Marie-Luise and Keim, Simon and Fabry, Ben and Virtanen, Sannakaisa}, doi = {10.1021/acsami.6b01747}, faupublication = {yes}, journal = {ACS Applied Materials and Interfaces}, keywords = {cell adhesion; corrosion protection; impedance spectroscopy; magnesium; organic coating}, pages = {11998-12006}, peerreviewed = {unknown}, title = {{Cell} {Adhesion} on {Surface}-{Functionalized} {Magnesium}}, volume = {8}, year = {2016} } @article{faucris.120222564, author = {Gerum, Richard and Richter, Sebastian and Fabry, Ben and Paranhos Zitterbart, Daniel}, doi = {10.1111/2041-210X.12702}, faupublication = {yes}, journal = {Methods in Ecology and Evolution}, peerreviewed = {unknown}, title = {{ClickPoints}: an expandable toolbox for scientific image annotation and analysis}, year = {2016} } @article{faucris.238603362, abstract = {We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that our method is accurate up to strains of 50% and remains valid even for irregularly shaped tissue samples when considering only the deformations in the far field. Finally, we demonstrate that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1 hr after seeding, while collective forces on longer timescales are guided by mechanical feedback from the extracellular matrix.}, author = {Mark, Christoph and Grundy, Thomas J. and Strissel, Pamela and Böhringer, David and Grummel, Nadine and Gerum, Richard and Steinwachs, Julian and Hack, Carolin and Beckmann, Matthias and Eckstein, Markus and Strick, Reiner and O'Neill, Geraldine M. and Fabry, Ben}, doi = {10.7554/eLife.51912}, faupublication = {yes}, journal = {eLife}, note = {CRIS-Team WoS Importer:2020-05-22}, peerreviewed = {unknown}, title = {{Collective} forces of tumor spheroids in three-dimensional biopolymer networks}, volume = {9}, year = {2020} } @article{faucris.274493512, author = {Mark, Christoph and Grundy, Thomas J. and Strissel, Pamela and Böhringer, David and Grummel, Nadine and Gerum, Richard and Steinwachs, Julian and Hack, Carolin and Beckmann, Matthias and Eckstein, Markus and Strick, Reiner and O'Neill, Geraldine M. and Fabry, Ben}, doi = {10.7554/eLife.59538}, faupublication = {yes}, journal = {eLife}, note = {EVALuna2:417751}, peerreviewed = {Yes}, title = {{Correction}: {Collective} forces of tumor spheroids in three-dimensional biopolymer networks.}, volume = {9}, year = {2020} } @article{faucris.240326581, abstract = {To reach the female gametophyte, growing pollen tubes must penetrate different tissues within the pistil, the female reproductive organ of a flower. Past research has identified various chemotropic cues that guide pollen tubes through the transmitting tract of the pistil, which represents the longest segment of its growth path. In addition, physical mechanisms also play a role in pollen tube guidance; however, these processes remain poorly understood. Here we show that pollen tubes from plants with solid transmitting tracts actively respond to the stiffness of the environment. We found that pollen tubes fromNicotiana tabacumand other plant species with a solid or semisolid transmitting tract increase their growth rate in response to an increasing matrix stiffness. By contrast, pollen tubes fromLilium longiflorumand other plant species with a hollow transmitting tract decrease their growth rate with increasing matrix stiffness, even though the forces needed to maintain a constant growth rate remain far below the maximum penetration force these pollen tubes are able to generate. Moreover, when confronted with a transition from a softer to a stiffer matrix, pollen tubes fromN. tabacumdisplay a greater ability to penetrate into a stiffer matrix compared with pollen tubes fromL. longiflorum,even though the maximum force generated by pollen tubes fromN. tabacum(11 mu N) is smaller than the maximum force generated by pollen tubes fromL. longiflorum(36 mu N). These findings demonstrate a mechano-sensitive growth behavior, termed here durotropic growth, that is only expressed in pollen tubes from plants with a solid or semisolid transmitting tract and thus may contribute to an effective pollen tube guidance within the pistil.}, author = {Reimann, Ronny and Kah, Delf-Thorge Eric and Mark, Christoph and Dettmer, Jan and Reimann, Theresa and Gerum, Richard and Geitmann, Anja and Fabry, Ben and Dietrich, Petra and Kost, Benedikt}, doi = {10.1104/pp.19.01505}, faupublication = {yes}, journal = {Plant Physiology}, note = {CRIS-Team WoS Importer:2020-07-10}, pages = {558-569}, peerreviewed = {Yes}, title = {{Durotropic} {Growth} of {Pollen} {Tubes}(1)([{OPEN}])}, volume = {183}, year = {2020} } @article{faucris.239210591, abstract = {To reach the female gametophyte, growing pollen tubes must penetrate different tissues within the pistil, the female reproductive organ of a flower. Past research has identified various chemotropic cues that guide pollen tubes through the transmitting tract of the pistil, which represents the longest segment of its growth path. In addition, physical mechanisms also play a role in pollen tube guidance; however, these processes remain poorly understood. Here we show that pollen tubes from plants with solid transmitting tracts actively respond to the stiffness of the environment. We found that pollen tubes from Nicotiana tabacum and other plant species with a solid or semisolid transmitting tract increase their growth rate in response to an increasing matrix stiffness. By contrast, pollen tubes from Lilium longiflorum and other plant species with a hollow transmitting tract decrease their growth rate with increasing matrix stiffness, even though the forces needed to maintain a constant growth rate remain far below the maximum penetration force these pollen tubes are able to generate. Moreover, when confronted with a transition from a softer to a stiffer matrix, pollen tubes from N. tabacum display a greater ability to penetrate into a stiffer matrix compared with pollen tubes from L. longiflorum, even though the maximum force generated by pollen tubes from N. tabacum (11 µN) is smaller than the maximum force generated by pollen tubes from L. longiflorum (36 µN). These findings demonstrate a mechano-sensitive growth behavior, termed here durotropic growth, that is only expressed in pollen tubes from plants with a solid or semisolid transmitting tract and thus may contribute to an effective pollen tube guidance within the pistil.
Animal sperm cells have the ability to freely swim by rhythmic movements of their flagella (Malo et al., 2006). By contrast, sperm cells of angiosperm plants have lost this ability (Dresselhaus et al., 2016) and are contained within the cytoplasm of the vegetative cell of a pollen grain. Upon germination, the vegetative pollen cell forms a long tubular protrusion, the pollen tube, which rapidly elongates through the pistil and transports the enclosed immobile sperm cells toward the egg cell and the central cell for double fertilization (Zhang et al., 2017).
As opposed to cell division, pollen tubes elongate by tip growth. This process depends on a fine-tuned interplay between turgor pressure and vesicle trafficking, which delivers material required for cell wall and plasma membrane extension exclusively to the pollen tube tip (Lord, 2000; Chebli et al., 2013; Hafidh et al., 2016a; Grebnev et al., 2017; Luo et al., 2017). Therefore, only the surface at the pollen tube tip changes its relative position with respect to the environment during cell elongation, giving rise to a low-friction and thus energetically favorable growth process that has also been observed in other invasively growing cell types, such as root hairs, fungal hyphae, and neurons (Palanivelu and Preuss, 2000; Sanati Nezhad and Geitmann, 2013). This mechanism enables pollen tubes of some plant species to grow at rates of more than 300 µm·min−1 (Williams et al., 2016), faster than any other plant cell (Shamsudhin et al., 2016).
To reach the female gametophyte, growing pollen tubes must penetrate different tissues within the pistil. After initial growth on the surface of the stigma, pollen tubes subsequently elongate through the transmitting tract within the style and the ovary, penetrate the septum epidermis to leave the transmitting tract, continue to elongate on the surface of the funiculus and through the micropyle of the ovule, and finally enter a synergid cell, where they burst and discharge their cytoplasm together with the enclosed sperm cells (Hulskamp et al., 1995; Crawford et al., 2007). Over the past two decades, many factors have been identified that are involved in the guidance of pollen tubes along their path toward the female gametophyte, including sugars, calcium ions, nitric oxide, lipids, and secreted peptides (Hulskamp et al., 1995; Ray et al., 1997; Wolters-Arts et al., 1998; Mollet et al., 2000; Higashiyama et al., 2003; Prado et al., 2004; Chae and Lord, 2011; Sanati Nezhad et al., 2014; Qu et al., 2015; Hafidh et al., 2016b; Higashiyama and Yang, 2017; Jiao et al., 2017). Most of these chemical signals guide the pollen tubes toward and inside the ovule following their emergence from the transmitting tract. However, the transmitting tract of the pistil typically represents the longest section of the pollen tube growth path in situ (de Graaf et al., 2003; Crawford and Yanofsky, 2008). Because chemical gradients are more difficult to maintain over longer distances, physical guidance mechanisms are thought to play an important role in directing pollen tube growth within the transmitting tract (Lennon et al., 1998; Lush et al., 2000), but this has so far not been characterized in detail.
Flowers of different plant species display a highly diverse pistil and transmitting tract anatomy, which complicates the investigation of physical pollen tube guidance. Within the transmitting tract of hollow (sometimes called “open”) styles, as observed for example in Lilium longiflorum flowers, pollen tubes grow on the epidermal surface of a cell-free canal filled with a viscous extracellular matrix (Sanders and Lord, 1992; de Graaf et al., 2001; Erbar, 2003). By contrast, the transmitting tract in solid (sometimes called “closed”) styles, as found in Arabidopsis (Arabidopsis thaliana) and Nicotiana tabacum flowers, is filled with tissue composed of cells embedded in an extracellular matrix, which pollen tubes need to penetrate (Lennon et al., 1998; Cheung et al., 2000; Erbar, 2003). The tissue within the transmitting tract imposes a substantial physical resistance on pollen tube growth (Agudelo et al., 2012), in particular as intercellular spaces in this tissue are typically smaller than the pollen tube diameter (Lennon et al., 1998; Roy et al., 1999; Cheung et al., 2000).
The maximum (or stalling) force that a growing pollen tube can generate to overcome the mechanical resistance restricting its expansion within pistil tissues is determined by the product of the hydrostatic turgor pressure and the cross-sectional area of the tube at its tip. Maximum forces generated by L. longiflorum tubes measured with capacitive force sensors (Burri et al., 2018) were found to be in the range of 9.6 ± 1.6 µN, whereas forces generated by Camellia japonica pollen tubes measured with soft microcantilevers (Ghanbari et al., 2018) were found to be around 1.5 µN. However, direct force measurements using capacitive force sensors or microcantilevers are technically highly demanding (Agudelo et al., 2013; Ghanbari et al., 2014; Sanati Nezhad et al., 2014). Moreover, measurements of the maximum stalling force cannot provide information on the penetration force of a pollen tube growing inside a pistil under physiological conditions, as this force depends on the growth rate and the mechanical impedance of the surrounding matrix (Sanati Nezhad et al., 2013).
In this study, we present a method to estimate the penetration force generated by a pollen tube tip during its growth through matrices of different stiffness. With this method, we investigated pollen tubes from plant species, both with hollow and with solid styles, and measured the relationship between penetration force and growth rate for matrices with different mechanical properties. We found that pollen tubes from plants with solid styles, but not those from plants with hollow styles, increase their growth rate in matrices with higher physical resistance, indicating that an active mechanosensory mechanism controls the tropic growth of these pollen tubes, which may help them to navigate through the complex architecture of the pistil to reach the female gametophyte. We propose the term durotropism for this mechanosensory mechanism that guides pollen tubes from plants with solid styles toward stiffer environments, analogous to the term durotaxis that describes the preferential migration of mammalian mesenchymal cells toward regions with higher substrate rigidity (Lo et al., 2000}, author = {Reimann, Ronny and Kah, Delf-Thorge Eric and Mark, Christoph and Dettmer, Jan and Reimann, Theresa and Gerum, Richard and Geitmann, Anja and Fabry, Ben and Dietrich, Petra and Kost, Benedikt}, doi = {10.1104/PP.19.01505}, faupublication = {yes}, journal = {Plant Physiology}, pages = {558-569}, peerreviewed = {Yes}, title = {{Durotropic} {Growth} of {Pollen} {Tubes}}, volume = {183}, year = {2020} } @article{faucris.107227604, author = {Gerum, Richard and Fabry, Ben and Metzner, Claus}, doi = {10.1371/journal.pone.0142490}, faupublication = {yes}, journal = {PLoS ONE}, pages = {e0142490}, peerreviewed = {Yes}, title = {{Emergence} of {Asynchronous} {Local} {Clocks} in {Excitable} {Media}}, volume = {10}, year = {2015} } @inproceedings{faucris.262683558, address = {NEW YORK}, author = {Eroles, Mar and Gerum, Richard and Fabry, Ben and Rico, Felix}, booktitle = {EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS}, faupublication = {yes}, note = {CRIS-Team WoS Importer:2021-08-13}, pages = {133-133}, peerreviewed = {unknown}, publisher = {SPRINGER}, title = {{Fast} phenotyping of monocytes mechanics under the cytokine storm}, year = {2021} } @article{faucris.315839256, abstract = {Cells cultured in 3D fibrous biopolymer matrices exert traction forces on their environment that induce deformations and remodeling of the fiber network. By measuring these deformations, the traction forces can be reconstructed if the mechanical properties of the matrix and the force-free matrix configuration are known. These requirements limit the applicability of traction force reconstruction in practice. In this study, we test whether force-induced matrix remodeling can instead be used as a proxy for cellular traction forces. We measure the traction forces of hepatic stellate cells and different glioblastoma cell lines and quantify matrix remodeling by measuring the fiber orientation and fiber density around these cells. In agreement with simulated fiber networks, we demonstrate that changes in local fiber orientation and density are directly related to cell forces. By resolving Rho-kinase (ROCK) inhibitor-induced changes of traction forces, fiber alignment, and fiber density in hepatic stellate cells, we show that the method is suitable for drug screening assays. We conclude that differences in local fiber orientation and density, which are easily measurable, can be used as a qualitative proxy for changes in traction forces. The method is available as an open-source Python package with a graphical user interface.}, author = {Böhringer, David and Bauer, Andreas and Moravec, Ivana and Bischof, Lars and Kah, Delf-Thorge Eric and Mark, Christoph and Grundy, Thomas J. and Görlach, Ekkehard and O'Neill, Geraldine M. and Budday, Silvia and Strissel, Pamela and Strick, Reiner and Malandrino, Andrea and Gerum, Richard and Mak, Michael and Rausch, Martin and Fabry, Ben}, doi = {10.1016/j.matbio.2023.11.004}, faupublication = {yes}, journal = {Matrix Biology}, keywords = {Biopolymer Networks; Fiber Orientation; Mechanobiology; Traction Force Microscopy}, note = {CRIS-Team Scopus Importer:2023-12-22}, pages = {39-48}, peerreviewed = {Yes}, title = {{Fiber} alignment in {3D} collagen networks as a biophysical marker for cell contractility}, volume = {124}, year = {2023} } @article{faucris.239475644, abstract = {Magnetic tweezers based on a solenoid with an iron alloy core are widely used to apply large forces (∼100 nN) onto micron-sized (∼5 μm) superparamagnetic particles for mechanical manipulation or microrheological measurements at the cellular and molecular level. The precision of magnetic tweezers, however, is limited by the magnetic hysteresis of the core material, especially for time-varying force protocols. Here, we eliminate magnetic hysteresis by a feedback control of the magnetic induction, which we measure with a Hall sensor mounted to the distal end of the solenoid core. We find that the generated force depends on the induction according to a power-law relationship and on the bead-tip distance according to a stretched exponential relationship. Combined, they describe with only three parameters the induction-force-distance relationship, enabling accurate force calibration and force feedback. We apply our method to measure the force dependence of the viscoelastic and plastic properties of fibroblasts using a protocol with stepwise increasing and decreasing forces. We group the measured cells in a soft and a stiff cohort and find that softer cells show an increasing stiffness but decreasing plasticity with higher forces, indicating a pronounced stress stiffening of the cytoskeleton. By contrast, stiffer cells show no stress stiffening but an increasing plasticity with higher forces. These findings indicate profound differences between soft and stiff cells regarding their protection mechanisms against external mechanical stress. In summary, our method increases the precision, simplifies the handling, and extends the applicability of magnetic tweezers.}, author = {Kah, Delf-Thorge Eric and Dürrbeck, Christopher and Schneider, Werner and Fabry, Ben and Gerum, Richard}, doi = {10.1016/j.bpj.2020.05.018}, faupublication = {yes}, journal = {Biophysical Journal}, note = {CRIS-Team Scopus Importer:2020-06-23}, peerreviewed = {Yes}, title = {{High}-{Force} {Magnetic} {Tweezers} with {Hysteresis}-{Free} {Force} {Feedback}}, year = {2020} } @article{faucris.107522404, author = {Bonakdar, Navid and Gerum, Richard and Kuhn, Michael and Spörrer, Marina and Lippert, Anna Helena and Schneider, Werner and Aifantis, Katerina E. and Fabry, Ben}, doi = {10.1038/nmat4689}, faupublication = {yes}, journal = {Nature Materials}, pages = {1090-4}, peerreviewed = {Yes}, title = {{Mechanical} plasticity of cells}, volume = {15}, year = {2016} } @article{faucris.222672289, author = {Schilling, Achim and Gerum, Richard and Krauß, Patrick and Metzner, Claus and Tziridis, Konstantin and Schulze, Holger}, doi = {10.3389/fnins.2019.00481}, faupublication = {yes}, journal = {Frontiers in Neuroscience}, peerreviewed = {Yes}, title = {{Objective} estimation of sensory thresholds based on neurophysiological parameters.}, year = {2019} } @article{faucris.222402193, abstract = {Reliable determination of sensory thresholds is the holy grail of signal detection theory. However, there exists no assumption-independent gold standard for the estimation of thresholds based on neurophysiological parameters, although a reliable estimation method is crucial for both scientific investigations and clinical diagnosis. Whenever it is impossible to communicate with the subjects, as in studies with animals or neonates, thresholds have to be derived from neural recordings or by indirect behavioral tests. Whenever the threshold is estimated based on such measures, the standard approach until now is the subjective setting-either by eye or by statistical means-of the threshold to the value where at least a “clear” signal is detectable. These measures are highly subjective, strongly depend on the noise, and fluctuate due to the low signal-to-noise ratio near the threshold. Here we show a novel method to reliably estimate physiological thresholds based on neurophysiological parameters. Using surrogate data we demonstrate that fitting the responses to different stimulus intensities with a hard sigmoid function, in combination with subsampling, provides a robust threshold value as well as an accurate uncertainty estimate. This method has no systematic dependence on the noise and does not even require samples in the full dynamic range of the sensory system. We prove that this method is universally applicable to all types of sensory systems, ranging from somatosensory stimulus processing in the cortex to auditory processing in the brain stem.}, author = {Schilling, Achim and Gerum, Richard and Krauß, Patrick and Metzner, Claus and Tziridis, Konstantin and Schulze, Holger}, doi = {10.3389/fnins.2019.00481}, faupublication = {yes}, journal = {Frontiers in Neuroscience}, keywords = {Auditory cortex; Auditory neuroscience; Automated threshold estimation; Electrophysiology; Hearing; Psychometric function; Somatosensation; Somatosensory cortex}, note = {CRIS-Team Scopus Importer:2019-07-16}, peerreviewed = {Yes}, title = {{Objective} estimation of sensory thresholds based on neurophysiological parameters}, volume = {13}, year = {2019} } @article{faucris.222398494, abstract = {The modulation of the acoustic startle reflex (ASR) by a pre-stimulus called pre-pulse inhibition (PPI, for gap of silence pre-stimulus: GPIAS) is a versatile tool to, e.g., estimate hearing thresholds or identify subjective tinnitus percepts in rodents. A proper application of these paradigms depends on a reliable measurement of the ASR amplitudes and an exact stimulus presentation in terms of frequency and intensity. Here, we introduce a novel open-source solution for the construction of a low-cost ASR setup. The complete software for data acquisition and stimulus presentation is written in Python 3.6 and is provided as an Anaconda package. Furthermore, we provide a construction plan for the sensor system based on low-cost hardware components. Exemplary GPIAS data from two animal models (Mus musculus, Meriones unguiculatus) show that the ratio histograms (1-GPIAS) of the gap-pre-stimulus and no pre-stimulus ASR amplitudes can be well described by a log-normal distribution being in good accordance to previous studies with already established setups. Furthermore, it can be shown that the PPI as a function of pre-stimulus intensity (threshold paradigm) can be approximated with a hard-sigmoid function enabling a reproducible sensory threshold estimation. Thus, we show that the open-source solution could help to further establish the ASR method in many laboratories and, thus, facilitate and standardize research in animal models of tinnitus and/or hearing loss.}, author = {Gerum, Richard and Rahlfs, Hinrich and Streb, Matthias and Krauß, Patrick and Grimm, Jannik and Metzner, Claus and Tziridis, Konstantin and Günther, Michael and Schulze, Holger and Kellermann, Walter and Schilling, Achim}, doi = {10.3389/fnbeh.2019.00140}, faupublication = {yes}, journal = {Frontiers in Behavioral Neuroscience}, keywords = {3D acceleration sensor; Anaconda package; Animal model; Low-cost setup; Startle; Tinnitus}, note = {CRIS-Team Scopus Importer:2019-07-16}, peerreviewed = {Yes}, title = {{Open}({G}){PIAS}: {An} open-source solution for the construction of a high-precision acoustic startle response setup for tinnitus screening and threshold estimation in rodents}, volume = {13}, year = {2019} } @article{faucris.279678122, abstract = {Emperor penguins (Aptenodytes forsteri) are highly adapted to the harsh conditions of the Antarctic winter: they are able to fast for up to 134 days during breeding. To conserve energy, emperor penguins form tight groups (huddles), which is key for their reproductive success. The effect of different meteorological factors on the huddling behaviour, however, is not well understood. Using time-lapse image recordings of an emperor penguin colony, we show that huddling can be described as a phase transition from a fluid to a solid state. We use the colony density as order parameter, and an apparent temperature that is perceived by the penguins as the thermodynamic variable. We approximate the apparent temperature as a linear combination of four meteorological parameters: ambient temperature, wind speed, global radiation and relative humidity. We find a wind chill factor of -2.9 °C (ms-1)-1, a humidity chill factor of -0.5 °C/%rel. humidity, and a solar radiation heating factor of 0.3 °C (Wm-2)-1. In the absence of wind, humidity and solar radiation, the phase transition temperature (50% huddling probability) is -48.2 °C for the investigated time period (May 2014). We propose that higher phase transition temperatures indicate a shrinking thermal insulation and thus can serve as a proxy for lower energy reserves of the colony, integrating pre-breeding foraging success at sea and energy expenditure at land due to environmental conditions. As current global change is predicted to have strong detrimental effects on emperor penguins within the next decades, our approach may thus contribute towards an urgently needed long-term monitoring system for assessing colony health.}, author = {Richter, Sebastian and Gerum, Richard and Winterl, Alexander and Houstin, A. and Seifert, Maria and Peschel, J. and Fabry, Ben and Le Bohec, Celine and Paranhos Zitterbart, Daniel}, doi = {10.1088/1361-6463/aabb8e}, faupublication = {yes}, journal = {Journal of Physics D: Applied Physics}, keywords = {climate variability; collective behaviour; emperor penguin; environmental conditions; huddling; phase transition}, note = {CRIS-Team Scopus Importer:2022-08-05}, peerreviewed = {Yes}, title = {{Phase} transitions in huddling emperor penguins}, volume = {51}, year = {2018} } @article{faucris.238881435, abstract = {Modern Machine learning techniques take advantage of the exponentially rising calculation power in new generation processor units. Thus, the number of parameters which are trained to solve complex tasks was highly increased over the last decades. However, still the networks fail – in contrast to our brain – to develop general intelligence in the sense of being able to solve several complex tasks with only one network architecture. This could be the case because the brain is not a randomly initialized neural network, which has to be trained from scratch by simply investing a lot of calculation power, but has from birth some fixed hierarchical structure. To make progress in decoding the structural basis of biological neural networks we here chose a bottom-up approach, where we evolutionarily trained small neural networks in performing a maze task. This simple maze task requires dynamic decision making with delayed rewards. We were able to show that during the evolutionary optimization random severance of connections leads to better generalization performance of the networks compared to fully connected networks. We conclude that sparsity is a central property of neural networks and should be considered for modern Machine learning approaches.}, author = {Gerum, Richard and Erpenbeck, André and Krauß, Patrick and Schilling, Achim}, doi = {10.1016/j.neunet.2020.05.007}, faupublication = {yes}, journal = {Neural Networks}, keywords = {Artificial neural networks; Biological plausibility; Evolution; Evolutionary algorithm; Maze task; Overfitting}, note = {CRIS-Team Scopus Importer:2020-06-02}, pages = {305-312}, peerreviewed = {Yes}, title = {{Sparsity} through evolutionary pruning prevents neuronal networks from overfitting}, volume = {128}, year = {2020} } @article{faucris.120221244, author = {Gerum, Richard and Richter, Sebastian and Fabry, Ben and Le Bohec, Céline and Bonadonna, Francesco and Nesterova, Anna and Paranhos Zitterbart, Daniel}, doi = {10.1088/1361-6463/aab46b}, faupublication = {yes}, journal = {Journal of Physics D-Applied Physics}, pages = {164004}, peerreviewed = {Yes}, title = {{Structural} organisation and dynamics in king penguin colonies}, volume = {51}, year = {2018} } @article{faucris.267256386, abstract = {Aims: Desminopathies comprise hereditary myopathies and cardiomyopathies caused by mutations in the intermediate filament protein desmin that lead to severe and often lethal degeneration of striated muscle tissue. Animal and single cell studies hinted that this degeneration process is associated with massive ultrastructural defects correlating with increased susceptibility of the muscle to acute mechanical stress. The underlying mechanism of mechanical susceptibility, and how muscle degeneration develops over time, however, has remained elusive. Methods: Here, we investigated the effect of a desmin mutation on the formation, differentiation, and contractile function of in vitro-engineered three-dimensional micro-tissues grown from muscle stem cells (satellite cells) isolated from heterozygous R349P desmin knock-in mice. Results: Micro-tissues grown from desmin-mutated cells exhibited spontaneous unsynchronised contractions, higher contractile forces in response to electrical stimulation, and faster force recovery compared with tissues grown from wild-type cells. Within 1 week of culture, the majority of R349P desmin-mutated tissues disintegrated, whereas wild-type tissues remained intact over at least three weeks. Moreover, under tetanic stimulation lasting less than 5 s, desmin-mutated tissues partially or completely ruptured, whereas wild-type tissues did not display signs of damage. Conclusions: Our results demonstrate that the progressive degeneration of desmin-mutated micro-tissues is closely linked to extracellular matrix fibre breakage associated with increased contractile forces and unevenly distributed tensile stress. This suggests that the age-related degeneration of skeletal and cardiac muscle in patients suffering from desminopathies may be similarly exacerbated by mechanical damage from high-intensity muscle contractions. We conclude that micro-tissues may provide a valuable tool for studying the organization of myocytes and the pathogenic mechanisms of myopathies.}, author = {Spörrer, Marina and Kah, Delf-Thorge Eric and Gerum, Richard and Reischl, Barbara and Huraskin, Danyil and Dessalles, Claire A. and Schneider, Werner and Goldmann, Wolfgang and Herrmann, Harald and Thievessen, Ingo and Clemen, Christoph S. and Friedrich, Oliver and Hashemolhosseini, Said and Schröder, Rolf and Fabry, Ben}, doi = {10.1111/nan.12784}, faupublication = {yes}, journal = {Neuropathology and Applied Neurobiology}, keywords = {desmin; desminopathy; micro-tissue; skeletal muscle physiology; tissue engineering}, note = {CRIS-Team Scopus Importer:2021-12-17}, peerreviewed = {Yes}, title = {{The} desmin mutation {R349P} increases contractility and fragility of stem cell-generated muscle micro-tissues}, year = {2021} } @article{faucris.120100684, author = {Gerum, Richard and Fabry, Ben and Metzner, Claus and Beaulieu, Michaël and Ancel, André and Paranhos Zitterbart, Daniel}, doi = {10.1088/1367-2630/15/12/125022}, faupublication = {yes}, journal = {New Journal of Physics}, peerreviewed = {Yes}, title = {{The} origin of traveling waves in an emperor penguin huddle}, volume = {35}, year = {2013} } @article{faucris.107241244, author = {Braniš, Jaroslav and Pataki, Csilla and Spörrer, Marina and Gerum, Richard and Mainka, Astrid and Cermak, Vladimir and Goldmann, Wolfgang and Fabry, Ben and Brabek, Jan and Rosel, Daniel}, doi = {10.1038/srep46233}, faupublication = {yes}, journal = {Scientific Reports}, pages = {46233}, peerreviewed = {Yes}, title = {{The} role of focal adhesion anchoring domains of {CAS} in mechanotransduction}, volume = {7}, year = {2017} } @article{faucris.107257744, author = {Braniš, Jaroslav and Pataki, Csilla and Spörrer, Marina and Gerum, Richard and Mainka, Astrid and Cermak, Vladimir and Goldmann, Wolfgang and Fabry, Ben and Brabek, Jan and Rosel, Daniel}, doi = {10.1038/srep46233}, faupublication = {yes}, journal = {Scientific Reports}, pages = {46233}, peerreviewed = {Yes}, title = {{The} role of focal adhesion anchoring domains of {CAS} in mechanotransduction}, volume = {7}, year = {2017} } @article{faucris.120140504, author = {Braniš, Jaroslav and Pataki, Csilla and Spörrer, Marina and Gerum, Richard and Mainka, Astrid and Cermak, Vladimir and Goldmann, Wolfgang and Fabry, Ben and Brabek, Jan and Rosel, Daniel}, doi = {10.1038/srep46233}, faupublication = {yes}, journal = {Scientific Reports}, pages = {46233}, peerreviewed = {Yes}, title = {{The} role of focal adhesion anchoring domains of {CAS} in mechhttps://cris.fau.de/converis/mypages/edit/{Publication}/1080200/default#anotransduction}, volume = {7}, year = {2017} } @article{faucris.217796713, abstract = {Background: Missense mutations in keratin 5 and 14 genes cause the severe skin fragility disorder epidermolysis bullosa simplex (EBS)by collapsing of the keratin cytoskeleton into cytoplasmic protein aggregates. Despite intense efforts, no molecular therapies are available, mostly due to the complex phenotype of EBS, comprising cell fragility, diminished adhesion, skin inflammation and itch. Methods: We extensively characterized KRT5 and KRT14 mutant keratinocytes from patients with severe generalized EBS following exposure to the chemical chaperone 4-phenylbutyrate (4-PBA). Findings: 4-PBA diminished keratin aggregates within EBS cells and ameliorated their inflammatory phenotype. Chemoproteomics of 4-PBA-treated and untreated EBS cells revealed reduced IL1β expression- but also showed activation of Wnt/β-catenin and NF-kB pathways. The abundance of extracellular matrix and cytoskeletal proteins was significantly altered, coinciding with diminished keratinocyte adhesion and migration in a 4-PBA dose-dependent manner. Interpretation: Together, our study reveals a complex interplay of benefits and disadvantages that challenge the use of 4-PBA in skin fragility disorders.}, author = {Spörrer, Marina and Prochnicki, Ania and Tölle, Regine C. and Nyström, Alexander and Esser, Philipp R. and Homberg, Melanie and Athanasiou, Ioannis and Zingkou, Eleni and Schilling, Achim and Gerum, Richard and Thievessen, Ingo and Winter, Lilli and Bruckner-Tuderman, Leena and Fabry, Ben and Magin, Thomas M. and Dengjel, Jörn and Schröder, Rolf and Kiritsi, Dimitra}, doi = {10.1016/j.ebiom.2019.04.062}, faupublication = {yes}, journal = {EBioMedicine}, keywords = {4-PBA; Epidermolysis bullosa; Keratinocyte; Keratins; Skin blistering}, note = {CRIS-Team Scopus Importer:2019-05-17}, peerreviewed = {Yes}, title = {{Treatment} of keratinocytes with 4-phenylbutyrate in epidermolysis bullosa: {Lessons} for therapies in keratin disorders}, year = {2019} } @article{faucris.284132881, abstract = {Numerous cell functions are accompanied by phenotypic changes in viscoelastic prop-erties, 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 µm wide microflu-idic channel. The fluid shear stress induces large, ear 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. Roscoe [1] 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.}, author = {Gerum, Richard and Mirzahossein, Elham and Eroles, Mar and Elsterer, Jennifer and Mainka, Astrid and Bauer, Andreas and Sonntag, Selina and Winterl, Alexander and Bartl, Johannes and Fischer, Lena and Abuhattum, Shada and Goswami, Ruchi and Girardo, Salvatore and Guck, Jochen and Schrüfer, Stefan and Ströhlein, Nadi and Nosratlo, Mojtaba and Herrmann, Harald and Schultheis, Dorothea and Rico, Felix and Müller, Sebastian Johannes and Gekle, Stephan and Fabry, Ben}, doi = {10.7554/eLife.78823}, faupublication = {yes}, journal = {eLife}, note = {CRIS-Team Scopus Importer:2022-10-28}, peerreviewed = {Yes}, title = {{Viscoelastic} properties of suspended cells measured with shear flow deformation cytometry}, volume = {11}, year = {2022} }