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Biology subjects

Schlegel, A.

Publications and source records attributed to Schlegel, A..

3 recordsLinked to original sources

Nanothermometry-enabled intelligent laser tissue soldering

While often life-saving, surgical resectioning of diseased tissues puts patients at risk for post-operative complications. Sutures and staples are well-accepted and routinely used to reconnect tissues, however, their mechanical mismatch with biological soft tissue and invasiveness contribute to wound healing complications, infections, and post-operative fluid leakage. In principle, laser tissue soldering offers an attractive, minimally-invasive alternative for seamless soft tissue fusion. However, despite encouraging experimental observations, including accelerated healing and lowered infection risk, critical issues related to temperature monitoring and control during soldering and associated complications have prevented their clinical exploitation to date. Here, we introduce intelligent laser tissue soldering (iSoldering) with integrated nanothermometry as a promising yet unexplored approach to overcoming the critical shortcomings of laser tissue soldering. We demonstrate that adding thermoplasmonic and nanothermometry nanoparticles to proteinaceous solders enables heat confinement and non-invasive temperature monitoring and control, offering a route to high-performance, leak-tight tissue sealing even at deep tissue sites. The resulting tissue seals exhibit excellent mechanical properties and resistance to chemically-aggressive digestive fluids, including gastrointestinal juice. The iSolder can be readily cut and shaped by surgeons to optimally fit the tissue defect and can even be applied using infrared light from a medically approved light source, hence fulfilling key prerequisites for application in the operating theatre. Overall, iSoldering enables reproducible and well-controlled high-performance tissue sealing, offering new prospects for its clinical exploitation in diverse fields ranging from cardiovascular to visceral and plastic surgery. TeaserIntelligent solders containing nanothermometers and thermoplasmonics offer new route to high-performance tissue sealing.

bioengineering↗

Highly potent anti-SARS-CoV-2 multi-DARPin therapeutic candidates

Globally accessible therapeutics against SARS-CoV-2 are urgently needed. Here, we report the generation of the first anti-SARS-CoV-2 DARPin molecules with therapeutic potential as well as rapid large-scale production capabilities. Highly potent multivalent DARPin molecules with low picomolar virus neutralization efficacies were generated by molecular linkage of three different monovalent DARPin molecules. These multivalent DARPin molecules target various domains of the SARS-CoV-2 spike protein, thereby limiting possible viral escape. Cryo-EM analysis of individual monovalent DARPin molecules provided structural explanations for the mode of action. Analysis of the protective efficacy of one multivalent DARPin molecule in a hamster SARS-CoV-2 infection model demonstrated a significant reduction of pathogenesis. Taken together, the multivalent DARPin molecules reported here, one of which has entered clinical studies, constitute promising therapeutics against the COVID-19 pandemic.

immunology↗

Multivariate directed connectivity analysis (MDCA) enables decoding of directed interactions in neural and social networks

Many scientific fields currently face the daunting task of studying the dynamics of complex networks. For example, while we know that the rich mental phenomena of humans and other animals are mediated by complex systems of neural circuits in the brain, the mechanistic links between these biological networks and the functions that they mediate are poorly understood. Here we present a novel class of methods, termed multivariate directed connectivity analysis, to investigate network dynamics via patterns of directed interactions between network nodes. We validate these methods using simulated data and apply them to three real-world datasets, two neuroscientific and one investigating the 2016 US presidential candidates influence on the social media service Twitter. We find that these methods enable novel understanding of how information processing is distributed across networks. The methods are generally applicable to the study of dynamic information networks in biological, computational, and other fields of research.

neuroscience↗