Biology subjects

Brosz, M.

Publications and source records attributed to Brosz, M..

3 recordsLinked to original sources

bioRxiv2024

ColBuilder: Flexible structure generation of crosslinked collagen fibrils

Collagen fibrils are fundamental building blocks of connective tissues, yet generating accurate molecular models of their structure remains challenging due to their hierarchical organization and complex crosslinking patterns. ColBuilder has been developed to automate the generation of atomistic models of crosslinked collagen fibrils and facilitate the setup of molecular simulations. The tool integrates homology modeling, higher-order structure generation and optimization to build complete fibril structures with precise control over sequence composition, crosslinking patterns, and dimensions. Users can explore different collagen sequences, manipulate crosslink chemistry through mixed ratios and densities, and generate fibrils of varying diameter and length. All-atom molecular dynamics simulations of 335 nm-long fibrils validate the generated structures, showing excellent agreement with experimental measurements of D-band periodicity and force-extension behavior. ColBuilder is available both as an open-source command-line application and through a web interface at colbuilder.mpip-mainz.mpg.de.

biophysics↗

bioRxiv2023

O-glycans Expand Lubricin and Attenuate its Viscosity and Shear Thinning

Lubricin, an intrinsically disordered glycoprotein, plays a pivotal role in facilitating smooth movement and ensuring the enduring functionality of synovial joints. The central domain of this protein serves as a source of this excellent lubrication, and is characterized by its highly glycosylated, negatively charged, and disordered structure. However, the influence of O-glycans on the viscosity of lubricin remains unclear. In this study, we employ molecular dynamics simulations in absence and presence of shear, along with continuum simulations, to elucidate the intricate interplay between O-glycans and lubricin and the impact of O-glycans on lubricins conformational properties and viscosity. We find the presence of O-glycans to induce a more extended conformation in fragments of the disordered region of lubricin. These O-glycans contribute to a reduction in solution viscosity but at the same time weaken shear thinning at high shear rates, compared to non-glycosylated systems with the same density. This effect is attributed to the steric and electrostatic repulsion between the fragments, which prevent their conglomeration and structuring. Our computational study yields a mechanistic mechanism underlying previous experimental observations of lubricin and paves the way to more rationally understanding its function in the synovial fluid.

biophysics↗

bioRxiv2023

Energetics and kinetics of membrane permeation of photoresists for bioprinting

Three-dimensional (3D) bioprinting is a promising technology which typically uses bioinks to pattern cells and their scaffolds. The selection of cytocompatible inks is critical for the printing success. In laserbased 3D bioprinting, photoresist molecules are used as bioinks. We propose that cytotoxicity can be a consequence of the interaction of photoresists with lipid membranes and their permeation into the cell. Here, molecular dynamics simulations and in vitro assays address this issue, retrieving partition coefficients, free energies, and permeabilities for eight commonly-used photoresists in model lipid bilayers. Crossing the hydrophobic center of the membrane constitutes the rate limiting step during permeation. In addition, three photoresists feature a preferential localization site at the acyl chain headgroup interface. Photoresist permeabilities range over eight orders of magnitude, with some molecules being membrane-permeable on bioprinting timescales. Moreover, permeation correlates well with the oil-water partition coefficients and is severely hampered by the lipid ordering imposed by the lipid saturation. Overall, the mechanism of interaction of photoresists with model lipid bilayers is provided here, helping to classify them according to their residence in the membrane and permeation through it. This is useful information to guide the selection of cytocompatible photoresists for 3D bioprinting.

biophysics↗