Debora Monego

Motivation: Collagen fibrils are the primary load-bearing units of connective tissues. However, generating atomistic, simulation-ready models remains challenging due to collagen’s hierarchical organization and the diversity of its crosslinking network across tissues, ages, and metabolic states. Notably, non-enzymatic advanced glycation end-product (AGE) crosslinks—central to aging and diabetic complications—are largely absent from current atomistic fibril modelling workflows. Results: Here, we present an extension of the ColBuilder framework to generate atomistic collagen fibril models that incorporate three representative AGE-derived crosslinks (glucosepane, pentosidine, and MOLD) alongside enzymatic crosslinks. Amber99-compatible parameters are provided and assessed against QM-optimized reference geometries using all-atom molecular dynamics (MD) simulations. As proof-of-concept, we examine the mechanical response of single D-period collagen microfibrils featuring enzymatic-only, AGE-only, and mixed crosslink patterns in molecular dynamics simulations under force, and observe that AGE crosslinks differently impact the fibril structure compared to enzymatic crosslinks. The extension to ColBuilder can aid future structure-based research on collagen aging. Availability and implementation: ColBuilder is available as an open-source Python command-line package at https://github.com/graeter-group/colbuilder.

Motivation: Collagen fibrils are the primary load-bearing units of connective tissues. However, generating atomistic, simulation-ready models remains challenging due to collagen’s hierarchical organization and the diversity of its crosslinking network across tissues, ages, and metabolic states. Notably, non-enzymatic advanced glycation end-product (AGE) crosslinks—central to aging and diabetic complications—are largely absent from current atomistic fibril modelling workflows. Results: Here, we present an extension of the ColBuilder framework to generate atomistic collagen fibril models that incorporate three representative AGE-derived crosslinks (glucosepane, pentosidine, and MOLD) alongside enzymatic crosslinks. Amber99-compatible parameters are provided and assessed against QM-optimized reference geometries using all-atom molecular dynamics (MD) simulations. As proof-of-concept, we examine the mechanical response of single D-period collagen microfibrils featuring enzymatic-only, AGE-only, and mixed crosslink patterns in Molecular Dynamics simulations under force, and observe that AGE crosslinks differently impact the fibril structure compared to enzymatic crosslinks. The extension to ColBuilder can aid future structure-based research on collagen aging. Availability and implementation: ColBuilder is available as an open-source Python command-line package at https://github.com/graeter-group/colbuilder .

Understanding how nanoparticles form stable colloids is fundamental to their practical applications. Nonlinear ligands are known to increase the stability of nanoparticles in apolar solvents compared to shells of linear alkyl chains. Here, we reveal the molecular origin of this colloidal stability. We observe that even a single methyl side chain can suppress disorder-order transitions in the ligand shell, with double bonds or branches leading to drastic decreases in agglomeration temperature in such dispersions. Through a combination of temperature-dependent X-ray scattering and molecular dynamics simulations, we show that these simple structural modifications prevent ligand molecules from forming ordered bundles, maintaining shell disorder even at temperatures approaching solvent freezing. The absence of ligand order enhances colloidal stability by weakening attraction between the ligand shells via a combination of energetic and entropic factors. This mechanism extends dispersion stability by more than 100 K compared to linear ligands of equivalent length. Our findings provide a molecular-level explanation for the enhanced stability previously observed with branched and unsaturated ligands, offering an effective strategy for engineering nanoparticle dispersions that remain stable across broad temperature ranges.

Motivation: 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. Results: 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 335nm-long fibrils validate the generated structures, showing excellent agreement with experimental measurements of D-band periodicity and force-extension behavior. Availability and implementation: ColBuilder is available both as an open-source command-line application and through a web interface at https://colbuilder.mpip-mainz.mpg.de.

The ability of thin materials to shape-shift is a common occurrence that leads to dynamic pattern formation and function in natural and man-made structures. However, harnessing this concept to rationally design inorganic structures at the nanoscale has remained far from reach due to a lack of fundamental understanding of the essential physical components. Here, we show that the interaction between organic ligands and the nanocrystal surface is responsible for the full range of chiral shapes seen in colloidal nanoplatelets. The adsorption of ligands results in incompatible curvatures on the top and bottom surfaces of the NPL, causing them to deform into helicoïds, helical ribbons, or tubes depending on the lateral dimensions and crystallographic orientation of the NPL. We demonstrate that nanoplatelets belong to the broad class of geometrically frustrated assemblies and exhibit one of their hallmark features: a transition between helicoïds and helical ribbons at a critical width. The effective curvature κ ¯ is the single aggregate parameter that encodes the details of the ligand/surface interaction, determining the nanoplatelets’ geometry for a given width and crystallographic orientation. The conceptual framework described here will aid the rational design of dynamic, chiral nanostructures with high fundamental and practical relevance.

Collagen is a force-bearing, hierarchical structural protein important to all connective tissue. In tendon collagen, high load even below macroscopic failure level creates mechanoradicals by homolytic bond scission, similar to polymers. The location and type of initial rupture sites critically decide on both the mechanical and chemical impact of these micro-ruptures on the tissue, but are yet to be explored. We here use scale-bridging simulations supported by gel electrophoresis and mass spectrometry to determine breakage points in collagen. We find collagen crosslinks, as opposed to the backbone, to harbor the weakest bonds, with one particular bond in trivalent crosslinks as the most dominant rupture site. We identify this bond as sacrificial, rupturing prior to other bonds while maintaining the material’s integrity. Also, collagen’s weak bonds funnel ruptures such that the potentially harmful mechanoradicals are readily stabilized. Our results suggest this unique failure mode of collagen to be tailored towards combatting an early onset of macroscopic failure and material ageing.

We report on the colloidal stability of nanoparticles with alkanethiol shells in apolar solvents. Small angle X-ray scattering and molecular dynamics simulations were used to characterize the interaction between nanoparticles in linear alkane solvents ranging from hexane to hexadecane, including 4 nm gold cores with hexadecanethiol shells and 6 nm cadmium selenide cores with octadecanethiol shells. We find that the agglomeration is enthalpically driven and that, contrary to what one would expect from classical colloid theory, the temperature at which the particles agglomerate increases with increasing solvent chain length. We demonstrate that the inverted trend correlates with the temperatures at which the ligands order in the different solvents, and show that the inversion is due to a combination of enthalpic and entropic effects that enhance the stability of the ordered ligand state as the solvent length increases. We also explain why cyclohexane is a better solvent than hexane, despite having very similar solvation parameters to hexadecane.

Inorganic nanoparticle cores are often coated with organic ligands to render them dispersible in apolar solvents. However, the effect of the ligand shell on the stability of the overall hybrid particle is not fully understood. In particular, it is not known how the length of an apolar alkyl ligand chain affects the stability of a nanoparticle dispersion against agglomeration. Here, we describe an unexpectedly nonlinear relation, with an inversion of the effect of ligand length on stability depending on core size. Small-Angle X-ray Scattering and molecular dynamics simulations were used to study the interactions between gold nanoparticles and between cadmium selenide nanoparticles passivated by alkanethiol ligands with 12 to 18 carbons in the solvent decane. We find that increasing the ligand length increases stability in the core-dominated regime but decreases it in the ligand-dominated regime. This inversion is connected to a recently discovered transition from ligand- to core-dominated agglomeration as the core diameter increases at constant ligand length. Our results provide a microscopic picture of the forces that determine the colloidal stability of apolar nanoparticles and explain why classical colloid theory fails.

Being able to predict and tune the colloidal stability of nanoparticles is essential for a wide range of applications, yet our ability to do so is currently poor due to a lack of understanding of how they interact with one another. Here, we show that the agglomeration of apolar particles is dominated by either the core or the ligand shell, depending on the particle size and materials. We do this by using Small-Angle X-ray Scattering and molecular dynamics simulations to characterize the interaction between hexadecanethiol passivated gold nanoparticles in decane solvent. For smaller particles, the agglomeration temperature and interparticle spacing are determined by ordering of the ligand shell into bundles of aligned ligands that attract one another and interdigitate. In contrast, the agglomeration of larger particles is driven by van der Waals attraction between the gold cores, which eventually becomes strong enough to compress the ligand shell. Our results provide a microscopic description of the forces that determine the colloidal stability of apolar nanoparticles and explain why classical colloid theory fails.