Publications by authors named "Schwille P"
Mitochondria play critical roles in regulating cell fate, with dysfunction correlating with the development of multiple diseases, emphasizing the need for engineered nanomedicines that cross biological barriers. Said nanomedicines often target fluctuating mitochondrial properties and/or present inefficient/insufficient cytosolic delivery (resulting in poor overall activity), while many require complex synthetic procedures involving targeting residues (hindering clinical translation). The synthesis/characterization of polypeptide-based cell penetrating diblock copolymers of poly-L-ornithine (PLO) and polyproline (PLP) (PLO-PLP, n:m ratio 1:3) are described as mitochondria-targeting nanocarriers.
View Article and Find Full Text PDFEmbryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM), and receptor-mediated endocytosis.
View Article and Find Full Text PDFCell membranes in bacteria are laterally polarized to produce specific environments for membrane proteins, e.g., proteins involved in cell division which accumulate at mid-cell or the cell poles.
View Article and Find Full Text PDFA key challenge for bottom-up synthetic biology is engineering a minimal module for self-division of synthetic cells. Actin-based cytokinetic rings are considered a promising structure to produce the forces required for the controlled excision of cell-like compartments such as giant unilamellar vesicles (GUVs). Despite prior demonstrations of actin ring targeting to GUV membranes and myosin-induced constriction, large-scale vesicle deformation has been precluded due to the lacking spatial control of these contractile structures.
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- Liquid-liquid phase separation is a key process in live cells, influencing how structures like bacterial chromatin are organized over time and space.
- This study focuses on using fluorescence correlation spectroscopy (FCS) as a method to measure partition coefficients in these systems, providing advantages over traditional microscopy techniques.
- The protocol outlined includes steps for preparing in vitro condensates, acquiring FCS data, and analyzing results, while also addressing common issues in measuring partition coefficients.
Article Synopsis
- Focal adhesions are assemblies formed around activated integrin receptors, and the study investigates how these structures maintain their flexible, liquid-like properties in the cell.
- Researchers reconstitute focal adhesion components, observing that proteins like talin and vinculin undergo liquid-liquid phase separation, particularly when interacting with specific membrane lipids.
- The findings suggest that lipid binding activates these proteins, leading to their clustering on membranes, which helps early focal adhesions stay organized yet dynamic, allowing for quick assembly and disassembly.
Article Synopsis
- * The authors propose a new method for screening ML-generated proteins using both computational models and experimental techniques, focusing on proteins that can create structured patterns within cells.
- * Their study demonstrates that a top candidate protein can effectively replace a natural gene in Escherichia coli, suggesting potential for future use of ML-designed proteins in synthetic biology.
Article Synopsis
- Nanofabrication has advanced significantly due to DNA origami, which helps create intricate nanoscale structures with potential new biological functions.
- A new method using the E.coli Min protein system allows for the rapid assembly of these DNA structures in about 30 minutes, greatly improving efficiency over older methods.
- This technique enables the creation of various patterns and complex designs, like core-shell patterns, and shows promise for future uses in fields such as plasmonics, catalysis, and molecular sensing.
Article Synopsis
- * The study focuses on how man-made light-activated rotary motors affect biological membranes, revealing significant mechanical changes, including membrane expansion when these motors are activated.
- * Key findings highlight that factors like motor concentration and membrane fluidity impact these changes, with continuous expansion observed as long as the motors are energized, providing insights for future applications in chemical biology.
Although cell membranes exist in excess of water under physiological conditions, there are a number of biochemical processes, such as adsorption of biomacromolecules or membrane fusion events, that require partial or even complete transient dehydration of lipid membranes. Even though the dehydration process is crucial for understanding all fusion events, still little is known about the structural adaptation of lipid membranes when their interfacial hydration layer is perturbed. Here, we present the study of the nanoscale structural reorganization of phase-separated, supported lipid bilayers (SLBs) under a wide range of hydration conditions.
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- DNA-PAINT-based single-particle tracking (DNA-PAINT-SPT) has improved observation times in lab experiments by reducing issues from fluorophore photobleaching.
- The current method is limited to imaging only one target at a time and cannot be used for live cell imaging.
- This report introduces a new dual-color DNA-PAINT-SPT method that enables simultaneous live cell tracking and quantification of protein interactions, showcasing better performance than traditional single-dye methods.
Article Synopsis
- Cell division is tightly regulated, and the PomX/PomY/PomZ protein complex in Myxococcus xanthus plays a key role in organizing cytokinetic ring formation via the tubulin homolog FtsZ.
- PomY forms liquid-like biomolecular condensates through phase separation, while PomX assembles into filaments to create a large cellular structure, ensuring the formation of one PomY condensate per cell.
- PomY condensates selectively attract FtsZ, initiating its polymerization and guiding the formation of the FtsZ-ring necessary for cell division, indicating similarities to how eukaryotic microtubules are nucleated, hinting at an ancient evolutionary mechanism.
The bottom-up reconstitution of proteins for their modular engineering into synthetic cellular systems can reveal hidden protein functions in vitro. This is particularly evident for the bacterial Min proteins, a paradigm for self-organizing reaction-diffusion systems that displays an unexpected functionality of potential interest for bioengineering: the directional active transport of any diffusible cargo molecule on membranes. Here, the MinDE protein system is reported as a versatile surface patterning tool for the rational design of synthetically assembled 3D systems.
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- DNA origami is a flexible nanoengineering tool used in fields like membrane physiology and biophysics, allowing for easy modification of DNA strands to create membrane-active devices.
- Biological membranes are crucial for cell structure and function, making them prime targets for DNA origami in synthetic biology and biomedical research.
- The chapter outlines experimental methods to study how DNA origami interacts with synthetic membrane models, providing protocols for creating lipid model membranes and using microscopy to characterize these interactions.
Article Synopsis
- The study investigates the challenges of evaluating protein structures within living cells, specifically focusing on the Interleukin-4 receptor alpha (IL-4Rα) and its interactions with a non-canonical amino acid called BCNK.
- Researchers developed a method called brightness-calibrated ratiometric imaging to visualize and quantify the reaction yield of BCNK incorporation and its interactions with fluorescent dyes.
- Findings showed that variations in click efficiency and binding affinity for IL-4Rα revealed structural changes in the protein, suggesting that the efficiency of the click reaction can provide valuable insights into protein dynamics and structure in their natural environment.
Article Synopsis
- Sphingolipids, a diverse type of lipid found in eukaryotic cell membranes, play a crucial role in organizing lipids into domains that affect membrane function.
- Researchers developed photoswitchable sphingolipids that can transition between liquid-ordered and disordered states when exposed to specific light wavelengths, allowing for control of their organization in membrane models.
- Investigations using advanced microscopy showed that different types of photoswitchable sphingolipids can either reduce or increase liquid-ordered domain areas upon light-induced isomerization, highlighting the importance of their structural properties in membrane dynamics.
Article Synopsis
- Growth and division of biological cells rely on complex reactions driven by proteins, but how early cells inherited components before proteins is still unclear.
- This study uses ribozymes, which are catalytic RNA molecules, to show that freezing and thawing solutions can convert inactive RNA precursors into active ribozymes within lipid vesicles.
- The findings suggest that the cyclic process of freezing and melting, likely present on early Earth, could have allowed early protocells to grow and divide while still enabling the replication of RNA inside new vesicles.
Article Synopsis
- Compartmentalization is essential for cellular processes, allowing biomolecules to interact at the right times and places through self-organization of lipids, nucleic acids, and proteins.
- By utilizing reversible RNA-based liquid-liquid phase separation within giant unilamellar vesicles, researchers developed a system that propagates RNA enzymatic reactions through freeze-thaw cycles.
- This study shows that condensation of RNA can speed up enzymatic reactions and that decondensed RNA allows for exchange of materials between vesicles, paving the way for controlled processes in minimal cell models.
MipZ caps the plus-end of FtsZ polymers to promote their rapid disassembly.
Proc Natl Acad Sci U S A
December 2022
The spatiotemporal regulation of cell division is a fundamental issue in cell biology. Bacteria have evolved a variety of different systems to achieve proper division site placement. In many cases, the underlying molecular mechanisms are still incompletely understood.
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- Reversible membrane targeting of proteins plays a crucial role in cellular interactions, particularly in signaling and polarization, making membrane switches important for minimal cell design.
- The study introduces cell-free prenylated protein synthesis (CFpPS), which allows for the synthesis and membrane targeting of proteins in one reaction mix by integrating the necessary prenylation components.
- Using CFpPS, researchers successfully reconstituted the prenylated protein Cdc42 and its regulatory partner, demonstrating its potential as a powerful tool for engineering complex functions like polarity induction in synthetic cells.
Article Synopsis
- Molecular machines like ATPases and motor proteins use the energy from chemical reactions to change shape and perform motion, primarily by hydrolyzing nucleotide triphosphates.
- The aim of nanotechnology is to create nanomachines that can replicate similar functions, speed, and precision as biological molecular machines.
- By merging DNA nanotechnology for precision with fast chemical reaction cycles from systems chemistry, researchers are developing DNA devices that can control their conformational states and perform specific functions.
Article Synopsis
- Single-molecule localization microscopy (SMLM) has transformed light microscopy by achieving high optical resolution, but accurately counting the number of individual molecules in complex assemblies remains challenging.
- Researchers developed an enhanced technique called lbFCS+, which eliminates the need for reference calibrations to accurately count molecule copy numbers within specific areas of a DNA-PAINT image.
- In experiments with DNA origami structures, lbFCS+ successfully determined the number of target molecules and their binding dynamics, allowing for the analysis of complex molecular structures and interactions.
Article Synopsis
- * Researchers constructed lipid-stabilized foams under thermal gradients to enhance RNA accumulation and oligomerization, simulating early life conditions through alternating wet and dry states.
- * Myristic acid was identified as an effective stabilizer, and the resulting foams facilitated molecular localization and the formation of RNA aggregates, indicating a promising avenue for studying early molecular evolution.