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Christoph F. Schmidt

Hertha Sponer Distinguished Professor of Physics
Physics
Box 90305, Durham, NC 27708
2316 French Family Science Center, Duke Box 90305, 124 Science Drive, Durham, NC 27708

Selected Presentations & Appearances


The cytoskeleton and shell mechanics in animal and bacterial cells - The Triangle Cytoskeleton Meeting · September 25, 2023 Keynote/Named Lecture The Triangle Cytoskeleton Meeting, Raleigh
Slender filament microrheology: Using shape fluctuations to characterize equilibrium and non-equilibrium materials - BIRS Workshop 23w5120 - Mechanics of Cells and Polymer Networks: Bridging Theory, Simulation and Experiment · September 10, 2023 - September 15, 2023 Invited Talk Banff International Research Station for Mathematical Innovation and Discovery, Banff, Canada

The mechanical properties of soft materials can be probed on small length scales by microrheology, commonly done by tracking embedded micrometer-sized beads. We here introduce filament-based microrheology (FMR) using high-aspect-ratio semi-flexible filaments as probes. Such quasi-1D probes are much less invasive than beads due to their small cross sections. By imaging transverse bending modes, we can simultaneously probe multiple length scales. As a proof of principle, we use semiflexible single-walled carbon nanotubes (SWNTs) as probes that can be accurately and rapidly imaged based on their stable near-IR fluorescence. We find that the viscoelastic properties of sucrose, polyethylene oxide, and hyaluronic acid solutions measured in this way are in good agreement with those measured by conventional micro- and macrorheology.
When probing cells, it can be advantageous to avoid introducing probe particles altogether. We show that one can directly use fluctuation analysis of native cytoskeletal filaments, in this case microtubules, to perform intracellular microrheology when filament properties are known. Alternatively, one can probe filament mechanics when the response properties of the embedding cytoplasm are known. The latter approach is useful because microtubule mechanics in living cells are believed to be regulated by post-translational modifications, but are extremely difficult to probe directly, while fluctuations are difficult to interpret because they are generated by active forces in a surrounding cytoplasm with poorly understood material properties. We discovered that polyglutamylation, a post-translational modification enriched on microtubule networks that need to withstand large mechanical forces such as those in axons or cilia, significantly increases microtubule stiffness in living cells.

Viscoelasticity of Cell Nucleus and Intranuclear Transport - 2023 Triangle Soft Matter Workshop · May 15, 2023 National Scientific Meeting Duke, UNC, NC State, UNC/Chapel Hill
In vivo measurements of embryonic tissue mechanics - 2023 Triangle Soft Matter Workshop · May 15, 2023 National Scientific Meeting Duke, UNC, NC State, UNC/Chapel Hill
A high-throughput pipeline for morphological and functional analysis of cardiomyocytes - 2023 DPG Spring Meeting · March 30, 2023 International Meeting or Conference German Physical Society, Dresden, Germany

Cardiomyopathies, diseases of the heart muscle, affect 1 in 500 adults in Western countries. Nevertheless, reliable knowledge about disease onset and pathogenesis is lacking. To develop effective treatment options for patients, a dynamic and quantitative understanding of cardiomyopathies is needed. We developed an assay in which individual stem-cell derived heart cells of a fluorescent sarcomere reporter cell line grow in a heart-like environment - while allowing for automated high-resolution and high-framerate imaging - using micropatterned polyacrylamide acid (PAA) gels. We analyze the time-course of cell morphology and function upon drug-induced or genetic interventions with our deep-learning-based SarcAsM (Sarcomere Analysis Multitool) software. The resulting multiparametric functional and structural trajectories of cardiac muscle cells can be used to gain novel dynamical perspectives on the time-course and interplay of structure and function in health and disease and might contribute to the discovery of novel treatments.

The cytoskeleton and shell mechanics in animal and bacterial cells - The Triangle Cytoskeleton Meeting · September 25, 2023 Keynote/Named Lecture The Triangle Cytoskeleton Meeting, Raleigh
Slender filament microrheology: Using shape fluctuations to characterize equilibrium and non-equilibrium materials - BIRS Workshop 23w5120 - Mechanics of Cells and Polymer Networks: Bridging Theory, Simulation and Experiment · September 10, 2023 - September 15, 2023 Invited Talk Banff International Research Station for Mathematical Innovation and Discovery, Banff, Canada

The mechanical properties of soft materials can be probed on small length scales by microrheology, commonly done by tracking embedded micrometer-sized beads. We here introduce filament-based microrheology (FMR) using high-aspect-ratio semi-flexible filaments as probes. Such quasi-1D probes are much less invasive than beads due to their small cross sections. By imaging transverse bending modes, we can simultaneously probe multiple length scales. As a proof of principle, we use semiflexible single-walled carbon nanotubes (SWNTs) as probes that can be accurately and rapidly imaged based on their stable near-IR fluorescence. We find that the viscoelastic properties of sucrose, polyethylene oxide, and hyaluronic acid solutions measured in this way are in good agreement with those measured by conventional micro- and macrorheology.
When probing cells, it can be advantageous to avoid introducing probe particles altogether. We show that one can directly use fluctuation analysis of native cytoskeletal filaments, in this case microtubules, to perform intracellular microrheology when filament properties are known. Alternatively, one can probe filament mechanics when the response properties of the embedding cytoplasm are known. The latter approach is useful because microtubule mechanics in living cells are believed to be regulated by post-translational modifications, but are extremely difficult to probe directly, while fluctuations are difficult to interpret because they are generated by active forces in a surrounding cytoplasm with poorly understood material properties. We discovered that polyglutamylation, a post-translational modification enriched on microtubule networks that need to withstand large mechanical forces such as those in axons or cilia, significantly increases microtubule stiffness in living cells.

Viscoelasticity of Cell Nucleus and Intranuclear Transport - 2023 Triangle Soft Matter Workshop · May 15, 2023 National Scientific Meeting Duke, UNC, NC State, UNC/Chapel Hill
In vivo measurements of embryonic tissue mechanics - 2023 Triangle Soft Matter Workshop · May 15, 2023 National Scientific Meeting Duke, UNC, NC State, UNC/Chapel Hill
A high-throughput pipeline for morphological and functional analysis of cardiomyocytes - 2023 DPG Spring Meeting · March 30, 2023 International Meeting or Conference German Physical Society, Dresden, Germany

Cardiomyopathies, diseases of the heart muscle, affect 1 in 500 adults in Western countries. Nevertheless, reliable knowledge about disease onset and pathogenesis is lacking. To develop effective treatment options for patients, a dynamic and quantitative understanding of cardiomyopathies is needed. We developed an assay in which individual stem-cell derived heart cells of a fluorescent sarcomere reporter cell line grow in a heart-like environment - while allowing for automated high-resolution and high-framerate imaging - using micropatterned polyacrylamide acid (PAA) gels. We analyze the time-course of cell morphology and function upon drug-induced or genetic interventions with our deep-learning-based SarcAsM (Sarcomere Analysis Multitool) software. The resulting multiparametric functional and structural trajectories of cardiac muscle cells can be used to gain novel dynamical perspectives on the time-course and interplay of structure and function in health and disease and might contribute to the discovery of novel treatments.

Tracking and comprehending single cell dynamics in Drosophila dorsal closure using machine learning - 2023 DPG Spring Meeting · March 27, 2023 International Meeting or Conference German Physical Society, Dresden, Germany

Dorsal closure in Drosophila melanogaster embryos is a key model system for cell sheet morphogenesis and wound healing. We pursue a data-driven approach to understand the emergence of organized behavior on tissue level from the stochastic dynamics of single cells across scales. We developed DeepTissue, a deep-learning-based algorithm to automatically and robustly detect and temporally track various single cell features: cell shapes, cell junction lengths, myosin intensities, and tissue topology. Epithelial cells in dorsal closure exhibit oscillations and contribute to progressive cell sheet movements, while showing a large variability in individual shapes, dynamics, and fates. Based on high-quality multi-parametric trajectories of 1000s of single cells, we use unsupervised machine learning techniques to detect and classify behavioral and structural phenotypes. Further we study how the behavior of single cells throughout closure is driven by deterministic and/or stochastic factors, with the aim to predict singular cell ingression events.

Coarse-grained simulations of bacterial cell-wall mechanics and failure under extreme conditions - 2023 APS March Meeting · March 6, 2023 International Meeting or Conference American Physical Society, Las Vegas

Bacterial cell walls have to contain high internal turgor pressures of ~1atm in gram-negative bacteria and >10 atm in gram-positive bacteria. At the same time the wall has to be continuously expanded while a bacterium grows. For most bacterial cell walls a covalently crosslinked polymer network, the peptidoglycan (PG) layer, provides mechanical toughness. The PG layer is a thin porous polymer network - made of rigid glycan strands crosslinked by flexible oligopeptides. Bacteria achieve mechanical toughness while the wall is growing by careful control of defect generation, material insertion and network repair mechanisms. Many antibiotics act by interfering with these mechanisms. In order to understand the mechanisms of mechanical wall failure under extreme challenges, we model the PG layer as an anisotropic elastic network composed of two types of nonlinear springs (glycans and oligopeptides) using parameters from E-coli. The model assigns different structural, linear and non-linear elastic properties to the network constituents: Glycan strands are rigid and long, while peptides are flexible and short. We characterize stress-strain relationships, anisotropy, pore size distributions, and failure susceptibility and geometry as a function of the crosslink density, length distribution of glycan strands and angular alignment.

Direct measurement of turgor pressure in E. coli and B. subtilis - 2023 APS March Meeting · March 6, 2023 International Meeting or Conference American Physical Society, Las Vegas

The ability to maintain turgor pressure, i.e. osmotic imbalance, across the cell envelope, is a requirement for

proper metabolism and growth in walled microbial cells. To date, turgor pressure has only been estimated or

indirectly measured, because direct access has been difficult due to small cell sizes. How turgor pressure

depends on external conditions such as osmolarity and nutrient content remains largely unknown. Here we

present a micromanipulation technique using an atomic force microscope (AFM) that allows us to directly

measure and track turgor pressure on a living bacterium. We compress single cells between a large bead and a

flat surface using an AFM cantilever. Measured forces and indentation depths are then used to determine turgor

pressure with the help of a mechanical model that describes the deformation of the cell. We report dependencies

on external osmolarities for E. coli and B. subtilis.

The secret life of sarcomeres: stochastic heterogeneity of sarcomeres in beating stem-cell-derived cardiomyocytes - APS March Meeting 2023 · March 5, 2023 - March 10, 2023 International Meeting or Conference American Physical Society, Las Vegas

Sarcomeres are the basic contractile units of cardiac muscle
cells. We cultured individual hiPSC-derived cardiomyocytes on
biomimetic patterned substrates. We automatically tracked
single sarcomere dynamics from high-speed confocal
recordings with a custom machine-learning tool. While
emergent cell-level contractions were smooth, we found highly
stochastic and heterogeneous motions of single sarcomeres.
Rigid mechanical constraints force sarcomeres into a tug-ofwar
like competition driving dynamic heterogeneity. Analysis of
a large data set (>1200 cells) indicates that sarcomere
heterogeneity is not caused by static non-uniformity among
sarcomeres (e.g., strong/weak units), but can be primarily
attributed to the stochastic and non-linear nature of sarcomere
dynamics. We show that a simple dynamic model reproduces
crucial experimental findings by assuming non-monotonic
force-velocity relations for single sarcomeres, as previously
predicted for ensembles of motor proteins. This led us to a
novel, active matter perspective on sarcomere motion, with
sarcomeres as interacting non-linear, stochastic agents.

Bacterial cell wall mechanics and mechanosensitive channels - Biology Seminar Series · October 18, 2021 Invited Talk Duke University, Dept. Biology, Duke University

Presentation of new research on mechanosensitivity in beacteria and fruit flies to biology faculty and students

The Mechanics of the Drosophila Mechanosensory Chordotonal Organ - Biological Physics/Physical Biology seminar series · September 24, 2021 Invited Talk American Physical Society, Division of Biological Physics, online

Presentation of research on Drosophila mechanosensory organs to a worldwide audience in the APS/BPPB online seminar series

Advanced imaging methods for cell and tissue mechanics - Advanced Optical Imaging Seminar · September 21, 2021 Invited Talk Duke University, Duke University

Report on recent applications of advanced imaging methods at the ALIS center

Mechanosensing in Drosophila: larval chordotonal organs - Physics Colloquium · September 7, 2021 Invited Talk Emory University, Emory University

Presentation of research results on Drosophila mechanosensory organs