Tailored Bisacylphosphane Oxides for Precise Induction of Oxidative Stress-Mediated Cell Death in Biological Systems
Karim Almahayni,
Jana Bachir Salvador,
Riccardo Conti,
Anna Widera,
Malte Spiekermann,
Daniel Wehner,
Hansjörg Grützmacher,
Leonhard Möckl
ACS Chemical Biology
20
77-85
(2024)
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Precise cell elimination within intricate cellular populations is hampered by issues arising from the multifaceted biological properties of cells and the expansive reactivity of chemical agents. Current chemical platforms are often limited by their complexity, toxicity, and poor physical/chemical properties. Here, we report on the synthesis of a structurally versatile library of chemically tunable bisacylphosphane oxides (BAPOs), which harnesses the spatiotemporal precision of light delivery, thereby establishing a universal strategy for on-demand, precise cellular ablation in vitro and in vivo.
Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae
Francois El-Daher,
Stephen J. Enos,
Louisa K. Drake,
Daniel Wehner,
Markus Westphal,
Nicola J. Porter,
Catherine G. Becker,
Thomas Becker
Life science alliance
8
(1)
e202403052
(2024)
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Wound closure after brain injury is crucial for tissue restoration but remains poorly understood at the tissue level. We investigated this process using in vivo observations of larval zebrafish brain injury. Our findings show that wound closure occurs within the first 24 h through global tissue contraction, as evidenced by live-imaging and drug inhibition studies. Microglia accumulate at the wound site before closure, and computational models suggest that their physical traction could drive this process. Depleting microglia genetically or pharmacologically impairs tissue repair. At the cellular level, live imaging reveals centripetal deformation of astrocytic processes contacted by migrating microglia. Laser severing of these contacts causes rapid retraction of microglial processes and slower retraction of astrocytic processes, indicating tension. Disrupting the lcp1 gene, which encodes the F-actin–stabilising protein L-plastin, in microglia results in failed wound closure. These findings support a mechanical role of microglia in wound contraction and suggest that targeting microglial mechanics could offer new strategies for treating traumatic brain injury.
Nonlinear dynamics of femtosecond laser interaction with the central nervous system in zebrafish
Soyeon Jun,
Andreas Herbst,
Kilian Scheffter,
Nora John,
Julia Kolb,
Daniel Wehner,
Hanieh Fattahi
Communications Physics
7
161
(2024)
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Understanding the photodamage mechanism underlying the highly nonlinear dynamic of femtosecond laser pulses at the second transparent window of tissue is crucial for label-free microscopy. Here, we report the identification of two cavitation regimes from 1030 nm pulses when interacting with the central nervous system in zebrafish. We show that at low repetition rates, the damage is confined due to plasma-based ablation and sudden local temperature rise. At high repetition rates, the damage becomes collateral due to plasma-mediated photochemistry. Furthermore, we investigate the role of fluorescence labels with linear and nonlinear absorption pathways in optical breakdown. To verify our findings, we examined cell death and cellular responses to tissue damage, including the recruitment of fibroblasts and immune cells after irradiation. These findings contribute to advancing the emerging nonlinear optical microscopy techniques and provide a strategy for inducing precise, and localized injuries using near-infrared femtosecond laser pulses.
Estimation of the mass density of biological matter from refractive index measurements
Conrad Möckel,
Timon Beck,
Sara Kaliman,
Shada Abuhattum Hofemeier,
Kyoohyun Kim,
Julia Kolb,
Daniel Wehner,
Vasily Zaburdaev,
Jochen Guck
The quantification of physical properties of biological matter gives rise to novel ways of understanding functional mechanisms. One of the basic biophysical properties is the mass density (MD). It affects the dynamics in sub-cellular compartments and plays a major role in defining the opto-acoustical properties of cells and tissues. As such, the MD can be connected to the refractive index (RI) via the well known Lorentz-Lorenz relation, which takes into account the polarizability of matter. However, computing the MD based on RI measurements poses a challenge, as it requires detailed knowledge of the biochemical composition of the sample. Here we propose a methodology on how to account for assumptions about the biochemical composition of the sample and respective RI measurements. To this aim, we employ the Biot mixing rule of RIs alongside the assumption of volume additivity to find an approximate relation of MD and RI. We use Monte-Carlo simulations and Gaussian propagation of uncertainty to obtain approximate analytical solutions for the respective uncertainties of MD and RI. We validate this approach by applying it to a set of well-characterized complex mixtures given by bovine milk and intralipid emulsion and employ it to estimate the MD of living zebrafish (Danio rerio) larvae trunk tissue. Our results illustrate the importance of implementing this methodology not only for MD estimations but for many other related biophysical problems, such as mechanical measurements using Brillouin microscopy and transient optical coherence elastography.
A universal strategy to induce oxidative stress-mediated cell death in biological systems
Leonhard Möckl,
Karim Almahayni,
Jana Bachir Salvador,
Riccardo Conti,
Anna Widera,
Malte Spiekermann,
Daniel Wehner,
Hansjörg Grützmacher
Research Square 10.21203/rs.3.rs-3753893/v1
(2024)
| Preprint
| PDF
Precise cell elimination within intricate cellular populations is hampered by issues arising from the multifaceted biological properties of cells and the expansive reactivity of chemical agents. Current platforms are often limited by their complexity, toxicity, and poor physical/chemical properties. Here, we integrate the spatio-temporal precision of light delivery and the structural versatility of bisacylphosphane oxides (BAPOs), establishing a universal strategy for on-demand, precise cellular ablation in vitro and in vivo.
Contact
Research Group Daniel Wehner
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen, Germany
