arXiv subjects

Liedewij Laan

Publications and source records attributed to Liedewij Laan.

5 recordsLinked to original sources

arXiv2026

Tunable supramolecular polymerization from protein charge heterogeneity and architecture

Multidomain proteins with flexible unstructured sequence regions are abundant in cellular signaling. This protein architecture enables self-assembly into supramolecular structures, but how structured interaction domains and overall protein architecture jointly regulate the assembly size, structure and kinetics remains unclear. Here we use the budding yeast protein Bem1 as a model multidomain system to show that supramolecular polymerization can be tuned by charge heterogeneity and protein architecture. We experimentally demonstrate that Bem1's isolated PB1 domain forms extended filaments, whereas full-length Bem1 forms substantially shorter assemblies, indicating that the PB1 domain drives assembly while the remaining protein architecture tunes filament length. To understand these observations, we develop minimal coarse-grained models approximating the PB1 as a polar 5-bead domain and the full-length Bem1 as a 6-bead model with an additional bead representing the remainder of Bem1. The weight distribution of supramolecular filaments assembled by the 5-bead model quantitatively follows reversible Flory-like polymerization theory, which is tunable within a narrow charge polarity regime. In contrast, the 6-bead model shifts chain-length distributions towards shorter polymers despite retaining the same driving domain. We show that this deviation arises from steric and geometric constraints imposed by the appended unstructured regions, where the rotational flexibility between the charge-polar structured domain and the unstructured region emerges as key physical parameter governing self-limited self-assembly. Together, our results establish charge polarity, protein architecture, and conformational flexibility as programmable control knobs for supramolecular polymerization and suggest a general framework for understanding how multidomain proteins assemble into tunable biomolecular structures.

cond-mat.soft↗

arXiv2026

Roadmap for Condensates in Cell Biology

Biomolecular condensates govern essential cellular processes yet elude description by traditional equilibrium models. This roadmap, distilled from structured discussions at a workshop and reflecting the consensus of its participants, clarifies key concepts for researchers, funding bodies, and journals. After unifying terminology that often separates disciplines, we outline the core physics of condensate formation, review their biological roles, and identify outstanding challenges in nonequilibrium theory, multiscale simulation, and quantitative in-cell measurements. We close with a forward-looking outlook to guide coordinated efforts toward predictive, experimentally anchored understanding and control of biomolecular condensates.

physics.bio-ph↗

arXiv2023

Optimality in superselective surface binding by multivalent DNA nanostars

Weak multivalent interactions govern a large variety of biological processes like cell-cell adhesion and virus-host interactions. These systems distinguish sharply between surfaces based on receptor density, known as superselectivity. Earlier experimental and theoretical work provided insights into the control of selectivity: Weak interactions and a high number of ligands facilitate superselectivity. Present experimental studies typically involve tens or hundreds of interactions, resulting in a high entropic contribution leading to high selectivities. However, if, and if so how, systems with few ligands, such as multi-domain proteins and virus binding to a membrane, show superselective behavior is an open question. Here, we address this question with a multivalent experimental model system based on star shaped branched DNA nanostructures (DNA nanostars) with each branch featuring a single stranded overhang that binds to complementary receptors on a target surface. Each DNA nanostar possesses a fluorophore, to directly visualize DNA nanostar surface adsorption by total internal reflection fluorescence microscopy (TIRFM). We observe that DNA nanostars can bind superselectively to surfaces and bind optimally at a valency of three. We quantitatively explain this optimum by extending the current theory with interactions between DNA nanostar binding sites (ligands). Our results add to the understanding of multivalent interactions, by identifying microscopic mechanisms that lead to optimal selectivity, and providing quantitative values for the relevant parameters. These findings inspire additional design rules which improve future work on selective targeting in directed drug delivery.

physics.bio-ph↗

arXiv2022

Evolved interactions stabilize many coexisting phases in multicomponent liquids

Phase separation has emerged as an essential concept for the spatial organization inside biological cells. However, despite the clear relevance to virtually all physiological functions, we understand surprisingly little about what phases form in a system of many interacting components, like in cells. Here, we introduce a new numerical method based on physical relaxation dynamics to study the coexisting phases in such systems. We use our approach to optimize interactions between components, similar to how evolution might have optimized the interactions of proteins. These evolved interactions robustly lead to a defined number of phases, despite substantial uncertainties in the initial composition, while random or designed interactions perform much worse. Moreover, the optimized interactions are robust to perturbations and they allow fast adaption to new target phase counts. We thus show that genetically encoded interactions of proteins provide versatile control of phase behavior. The phases forming in our system are also a concrete example of a robust emergent property that does not rely on fine-tuning the parameters of individual constituents.

physics.bio-ph↗

arXiv2021

Direct visualization of superselective colloid-surface binding mediated by multivalent interactions

Reliably distinguishing between cells based on minute differences in receptor density is crucial for cell-cell or virus-cell recognition, the initiation of signal transduction and selective targeting in directed drug delivery. Such sharp differentiation between different surfaces based on their receptor density can only be achieved by multivalent interactions. Several theoretical and experimental works have contributed to our understanding of this "superselectivity", however a versatile, controlled experimental model system that allows quantitative measurements on the ligand-receptor level is still missing. Here, we present a multivalent model system based on colloidal particles equipped with surface-mobile DNA linkers that can superselectively target a surface functionalized with the complementary mobile DNA-linkers. Using a combined approach of light microscopy and Foerster Resonance Energy Transfer (FRET), we can directly observe the binding and recruitment of the ligand-receptor pairs in the contact area. We find a non-linear transition in colloid-surface binding probability with increasing ligand or receptor concentration. In addition, we observe an increased sensitivity with weaker ligand-receptor interactions and we confirm that the time-scale of binding reversibility of individual linkers has a strong influence on superselectivity. These unprecedented insights on the ligand-receptor level provide new, dynamic information into the multivalent interaction between two fluidic membranes mediated by both mobile receptors and ligands and will enable future work on the role of spatial-temporal ligand-receptor dynamics on colloid-surface binding.

cond-mat.soft↗