Marcel Sperling

A method for fabricating anisotropic monodisperse silicon dioxide (SiO ₂ ) patchy microspheres is developed. In the protocol, we utilize a modified microcontact printing (µCP) technique, employing a polydimethylsiloxane (PDMS) elastomer with a regularly grooved surface topography as a stamp. The stamp's microscale channels create a confined environment for the SiO ₂ microspheres, as they match the particle dimensions (≈4 µm). The solid‐phase µCP routine allows for the transfer of functional trialkoxysilanes from the stamp to the particles exclusively at their contact faces. By applying a second stamp to the exposed side of the particles, a fourth patch with different chemical information is added, resulting in particles with four equidistant patches along the particle equator. This fabrication process, compatible with a manifold follow‐up chemistry, adds patches with adjustable characteristics. Consequently, a polymeric material containing the nucleobase adenine, is successfully added to the patches, which enables interactions with materials that possess its complementary base uracil. The method is suitable to fabricate particles possessing a C _4v and C _2v symmetry. Importantly, the protocol is easily adaptable to other particle dimensions and surface chemistry, possessing significant potential in the field of anisotropically functionalized spherical colloidal particles.

We developed a method for fabricating anisotropic monodisperse silicon dioxide (SiO2) patchy microspheres. The protocol utilizes a modified microcontact printing (µCP) technique, employing a polydimethylsiloxane (PDMS) elastomer with a regularly grooved surface topography as a stamp. The stamp’s microscale channels create a confined environment for the SiO2 microspheres, as they match the particle dimensions (~4 µm). Our solid-phase µCP routine allows for the transfer of functional trialkoxysilanes from the elastomer stamp to the particles exclusively at their contact faces. By applying a second stamp to the exposed side of the particles, a fourth patch with different chemical information is added. This fabrication process, compatible with various follow-up chemistries, adds patches with adjustable characteristics. The method is suitable to fabricate particles possessing a C4v and C2v symmetry. Importantly, the protocol is easily adaptable to other particle dimensions and surface chemistries, indicating significant potential in the field of anisotropically functionalized spherical colloidal particles.

Protein–protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays or AlphaFold-Multimer predictions. Using the quantitative assay LuTHy together with our machine learning algorithm, we identified high-confidence interactions among SARS-CoV-2 proteins for which we predicted three-dimensional structures using AlphaFold-Multimer. We employed VirtualFlow to target the contact interface of the NSP10-NSP16 SARS-CoV-2 methyltransferase complex by ultra-large virtual drug screening. Thereby, we identified a compound that binds to NSP10 and inhibits its interaction with NSP16, while also disrupting the methyltransferase activity of the complex, and SARS-CoV-2 replication. Overall, this pipeline will help to prioritize PPI targets to accelerate the discovery of early-stage drug candidates targeting protein complexes and pathways.

Separation of particles by size, morphology, or material identity is of paramount importance in fields such as filtration or bioanalytics. Up to now separation of particles distinguished solely by surface properties or bulk/surface morphology remains a very challenging process. Here a combination of pressure‐driven microfluidic flow and local self‐phoresis/osmosis are proposed via the light‐induced chemical activity of a photoactive azobenzene‐surfactant solution. This process induces a vertical displacement of the sedimented particles, which depends on their size and surface properties . Consequently, different colloidal components experience different regions of the ambient microfluidic shear flow. Accordingly, a simple, versatile method for the separation of such can be achieved by elution times in a sense of particle chromatography. The concepts are illustrated via experimental studies, complemented by theoretical analysis, which include the separation of bulk‐porous from bulk‐compact colloidal particles and the separation of particles distinguished solely by slight differences in their surface physico‐chemical properties.