Publications by authors named "Matthias D Koch"

Article Synopsis
  • Type IV pili (T4P) are structures on the surface of gram-negative bacteria that enable various functions such as attaching to surfaces, forming biofilms, and moving around.
  • * A protein called PlzR was found to inhibit the assembly of T4P in Pseudomonas aeruginosa, affecting how the bacteria can be infected by certain bacteriophages.
  • * PlzR binds to a T4P chaperone called PilZ, disrupting the proper assembly of T4P by influencing an ATPase named PilB, and its expression is regulated by levels of cyclic di-GMP.
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Article Synopsis
  • * Researchers utilized biophysical simulations and microfluidic experiments, finding that increased fluid flow helps overcome bacterial resistance to various antimicrobials by enhancing their delivery.
  • * The study highlights the importance of combining physical flow with chemical dosage in developing effective antimicrobials, suggesting that this strategy could be crucial in combating rising antimicrobial resistance.
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More and more isolates have become resistant to antibiotics like carbapenem. As a consequence, ranks in the top three of pathogens for which the development of novel antibiotics is the most crucial. The pathogen causes both acute and chronic infections, especially in patients who are the most vulnerable.

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Fluid flow is thought to prevent bacterial adhesion, but some bacteria use adhesins with catch bond properties to enhance adhesion under high shear forces. However, many studies on bacterial adhesion either neglect the influence of shear force or use shear forces that are not typically found in natural systems. In this study, we use microfluidics and single-cell imaging to examine how the human pathogen interacts with surfaces when exposed to shear forces typically found in the human body (0.

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Bacterial populations are highly adaptive. They can respond to stress and survive in shifting environments. How the behaviours of individual bacteria vary during stress, however, is poorly understood.

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Colonies of the social bacterium go through a morphological transition from a thin colony of cells to three-dimensional droplet-like fruiting bodies as a strategy to survive starvation. The biological pathways that control the decision to form a fruiting body have been studied extensively. However, the mechanical events that trigger the creation of multiple cell layers and give rise to droplet formation remain poorly understood.

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Bacterial pathogenicity relies on both firm surface adhesion and cell dissemination. How twitching bacteria resolve the fundamental contradiction between adhesion and migration is unknown. To address this question, we employ live-cell imaging of type-IV pili (T4P) and therewith construct a comprehensive mathematical model of migration.

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Article Synopsis
  • - Cells in natural environments are affected by fluid flow, but most lab experiments, which use batch cell culture, overlook this factor in studying cell behavior and physiology.
  • - Research using microfluidics and single-cell imaging reveals that the combination of fluid flow (shear rate) and chemical stress from hydrogen peroxide affects how human pathogens respond at a genetic level, in ways not seen in standard lab settings.
  • - High shear rates in flowing conditions can significantly increase cells' sensitivity to low levels of hydrogen peroxide, aligning experimental conditions more closely with those in the human bloodstream, which helps explain how bacteria adapt to their natural environments.
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A brief history of optical forces, the invention of optical tweezers, and their application to biological problems.

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The ability of eukaryotic cells to differentiate surface stiffness is fundamental for many processes like stem cell development. Bacteria were previously known to sense the presence of surfaces, but the extent to which they could differentiate stiffnesses remained unclear. Here we establish that the human pathogen Pseudomonas aeruginosa actively measures surface stiffness using type IV pili (TFP).

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Type IV pili (TFP) function through cycles of extension and retraction. The coordination of these cycles remains mysterious due to a lack of quantitative measurements of multiple features of TFP dynamics. Here, we fluorescently label TFP in the pathogen and track full extension and retraction cycles of individual filaments.

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Pseudomonas aeruginosa is a significant threat in both healthcare and industrial biofouling. Surface attachment of P. aeruginosa is particularly problematic as surface association induces virulence and is necessary for the ensuing process of biofilm formation, which hampers antibiotic treatments.

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Mechanical properties of the extracellular matrix are important determinants of cellular migration in diverse processes, such as immune response, wound healing, and cancer metastasis. Moreover, recent studies indicate that even bacterial surface colonization can depend on the mechanics of the substrate. Here, we focus on physical mechanisms that can give rise to substrate-rigidity dependent migration.

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Multiple cell types sense fluid flow as an environmental cue. Flow can exert shear force (or stress) on cells, and the prevailing model is that biological flow sensing involves the measurement of shear force. Here, we provide evidence for force-independent flow sensing in the bacterium Pseudomonas aeruginosa.

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The wall-less, helical bacterial genus Spiroplasma has a unique propulsion system; it is not driven by propeller-like flagella but by a membrane-bound, cytoplasmic, linear motor that consists of a contractile chain of identical proteins spanning the entire cell length. By a coordinated spread of conformational changes of the proteins, kinks propagate in pairs along the cell body. However, the mechanisms for the initiation or delay of kinks and their coordinated spread remain unclear.

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Mechanical manipulation of single cytoskeleton filaments and their monitoring over long times is difficult because of fluorescence bleaching or phototoxic protein degradation. The integration of label-free microscopy techniques, capable of imaging freely diffusing, weak scatterers such as microtubules (MTs) in real-time, and independent of their orientation, with optical trapping and tracking systems, would allow many new applications. Here, we show that rotating-coherent-scattering microscopy (ROCS) in dark-field mode can also provide strong contrast for structures far from the coverslip such as arrangements of isolated MTs and networks.

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From colony formation in bacteria to wound healing and embryonic development in multicellular organisms, groups of living cells must often move collectively. Although considerable study has probed the biophysical mechanisms of how eukaryotic cells generate forces during migration, little such study has been devoted to bacteria, in particular with regard to the question of how bacteria generate and coordinate forces during collective motion. This question is addressed here using traction force microscopy.

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The transfer of mechanical signals through cells is a complex phenomenon. To uncover a new mechanotransduction pathway, we study the frequency-dependent transport of mechanical stimuli by single microtubules and small networks in a bottom-up approach using optically trapped beads as anchor points. We interconnected microtubules to linear and triangular geometries to perform micro-rheology by defined oscillations of the beads relative to each other.

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Thirty years after their invention by Arthur Ashkin and colleagues at Bell Labs in 1986 [1], optical tweezers (or traps) have become a versatile tool to address numerous biological problems. Put simply, an optical trap is a highly focused laser beam that is capable of holding and applying forces to micron-sized dielectric objects. However, their development over the last few decades has converted these tools from boutique instruments into highly versatile instruments of molecular biophysics.

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