Biology subjects

Van Hest, J.

Publications and source records attributed to Van Hest, J..

3 recordsLinked to original sources

bioRxiv2025

Topology Determines DNA Origami Diffusion in Intestinal Mucus

Efficient nanomedicine delivery across mucosal barriers remains a challenge, due to the complex and poorly understood relationship between nanoparticle design and mucus transport. Here, we present DNA origami as a platform to investigate how nanoparticle shape and ligand patterning influence diffusivity in mucus. By decoupling these parameters while maintaining identical material composition, we systematically evaluated the diffusion of rod, icosahedral, and rectangular nanostructures using high-resolution single-particle tracking. Our results reveal that diffusivity in mucus is not solely determined by shape or functionalization alone, but by their interplay: while unmodified rods diffused poorly, their mobility increased significantly upon antibody functionalization, reaching a maximum at an intermediate ligand density. In contrast, rods and icosahedra exhibited less pronounced and non-optimal responses to surface modification. These findings highlight the importance of topology-specific optimization in nanoparticle design and demonstrate the utility of DNA nanotechnology to uncover design rules for next generation mucus-penetrating drug delivery systems.

bioengineering↗

bioRxiv2024

Dynamically arrested condensate fusion creates complex structures with varying material properties

The cell nucleus and cytosol contain numerous biomolecular condensates which dynamically reshape, fuse and split to accomplish precise compartmentalization of the cell material. While it has been observed that some condensates rapidly coalesce, some others only attach to each other, or do not establish persistent interactions over time. Here, we explain these observations through optical tweezers and Molecular Dynamics simulations focusing on two condensate-forming, RNA-binding proteins--FUS and G3BP1--strongly involved in RNA metabolism and stress responses. We find that the fusion of pure droplets formed by these proteins can give rise to multiphase single-component condensates exhibiting notably different densities, architectures, and material properties. Such behaviour is dictated by the relative timescales of condensate fusion and protein internal mixing. A critical parameter controlling this interplay is the extent of ageing that condensates display; e.g., their progressive hardening driven by the accumulation of inter-protein {beta}-sheet assemblies over time. Strikingly, different degrees of ageing in fusing droplets can lead single-component condensates to form diverse architectures including concentric drops or two-sided condensates. Overall, our results highlight a mechanism, based on the temporal coupling between ageing, fusion, and mixing rate, by which biomolecular condensates form multiphasic structures with markedly different material properties, and hence potentially distinct biological roles.

biophysics↗

bioRxiv2019

Myosin II isoforms play distinct roles in adherens junction biogenesis

Adherens junction (AJ) assembly under force is essential for many biological processes like epithelial monolayer bending, collective cell migration, cell extrusion and wound healing. The acto-myosin cytoskeleton acts as a major force-generator during the de novo formation and remodelling of AJ. Here, we investigated the role of myosinII isoforms in epithelial junction assembly. Myosin IIA (NMIIA) and Myosin IIB (NMIIB) differentially regulate biogenesis of adherens junction through association with distinct actin networks. Analysis of junction dynamics, actin organization, and mechanical forces of control and knockdown cells for myosins revealed that NMIIA provides the mechanical tugging force necessary for cell-cell junction reinforcement and maintenance. NMIIB is involved in E-cadherin clustering, maintenance of a branched actin layer connecting E-cadherin complexes and perijunctional actin fibres leading to the building-up of anisotropic stress. These data reveal unanticipated complementary functions of NMIIA and NMIIB in the biogenesis and integrity of AJ.

cell biology↗